In October, at BCRF’s annual Symposium and Awards Luncheon, more than 250 esteemed BCRF-supported investigators were recognized for their achievements in breast cancer research and their devotion to ending breast cancer. The event also announced the Foundation’s research investment for the coming year.

This year’s program included an extraordinary symposium, “Three Decades of Innovation and Progress,” featuring an expert panel of BCRF investigators who discussed current breaking topics in breast cancer research and what’s new on the horizon.

The panel was co-moderated by BCRF Founding Scientific Director Dr. Larry Norton of Memorial Sloan Kettering Cancer Center and BCRF Scientific Director Dr. Judy E. Garber of Dana-Farber Cancer Institute and Harvard Medical School. Joining Drs. Norton and Garber were symposium panelists, Dr. Constance D. Lehman, Dr. Seema Khan, and Dr. Olufunmilayo I. Olopade, who received the 2023 Jill Rose Award for Scientific Excellence.

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Read the transcript below: 

Dr. Larry Norton: This is one of the most fun things that we do all year because this is our chance to speak about our work, to speak about breast cancer in general, to have contact with all of you who are obviously supporters, but also a chance for our array of investigators.

We have 150 in New York. We had a meeting yesterday to answer questions about their area of expertise and other questions that came up as well. So we have a sterling panel today. Of course, you see our scientific director, Judy Garber is sitting right there, and next to her is Funmi Olopade. I always have problems knowing where to put the accent. But it’s Connie Lehman and Seema Khan. I’m going to let themselves introduce themselves, their institution and their interests, and speak a little bit about their work.

We’ll start with Funmi—this is what we call her—who is the recipient of the Jill Rose Award this year, which is the highest honor that we give to an investigator every year, or to a scientist clinician who has made a very significant contribution to the field. And the list of contributions Funmi has made is so legion that again, it would eat up the entire time if we gave her a chance, if I started to roll through that. We’re very honored to have her here.

And then my other colleagues who are luminaries in their field will talk about their work, and then we’ll have a discussion, open up to your questions and discuss it among ourselves. I always like to think of this as very interactive and any questions you have, anything related to breast cancer, it doesn’t have to be the topics that we’re going to be talking about, is entirely appropriate to answer. And if I can’t answer the questions, Judy is here and she’s going to save me. So let’s take it away. Funmi, let’s start with you.

Dr. Olufunmilayo I. Olopade: Good morning, and thank you so much to the Scientific Advisory Board for naming me the Jill Rose Award winner for this year. And it’s always wonderful for me to come to New York because I live in Chicago. It was that second city, but now I’m even told it’s a third city because we’re always looking to be better than New York. And my work has actually gotten me to think about how we organize cities because I came to Chicago 40 years ago and our city is organized south, north, west, and east, and I live on the south side of Chicago, the best place to live on the planet. But also a place that’s segregated and a place where the University of Chicago has been working hard to make sure that every researcher, all research we do has global impact. And thinking about global impact of our work, I see patients who come to my clinic and they come in different shapes, sizes, colors. I work in genetics.

I was very fascinated about genetics and I happened to have married a man who is very concerned about the environment because our first daughter had asthma. And so every time we’re in the clinic and we’re seeing different types of patients, the question we ask is, “Are they having a severe form of asthma or breast cancer because they’re black or is it because we haven’t really had a good understanding of the root causes of every chronic illness?” And so we’re adult doctors, but our patients actually really teach us a lot. And so when I joined up with my colleagues who were looking to get a better understanding of the genetic basis of breast cancer, that’s when I ran into my amazing colleague Mary-Claire King. And we wanted to know, the families with breast cancer that come from different parts of the city of Chicago, what’s the origin of their breast cancer?

Why are they getting breast cancer at 30, at 25, at 21? And why do some old ladies on the south side of Chicago live with their breast cancer and they won’t show up to our emergency room until it’s coming out of their breast? And so I began to ask, “Is this America, and why is it so diverse in terms of the questions that we can ask?” So that’s why we began really thinking about who has BRCA1, BRCA2, and who doesn’t have a genetic reason for their breast cancer and how can we study the fundamental questions of why does a woman get breast cancer? And the answer is, the most important risk factor is you are a woman, and whether we know why you got the breast cancer or not, we ought to be able to treat you effectively. So that’s why I then started asking why are some people living and doing really well, surviving with great quality of life, and some don’t even make it to one year after a diagnosis of breast cancer?

So I’ve joined up with a lot of amazing people to ask those questions. What should we do to treat every patient successfully so that not only do they survive, but they thrive after a diagnosis of breast cancer? And my work is taking me to Nigeria and back and the lessons I’ve learned, it’s really been powerful to be able to think about all of us and the promise of precision medicine. So in a nutshell, that’s what I do and I’m passionate about it and I can’t thank all of you who support BCRF enough for giving us the idea to ask any question and to be creative with our research. Thank you.

Dr. Norton: Connie.

Dr. Constance D. Lehman: Good morning. I’m Connie Lehman. I’m just delighted to be here. I’m a breast imager in Boston at Mass General and Harvard, and I am so grateful for the Breast Cancer Research Foundation’s willingness to fund and support high-risk, cutting edge, future-thinking research. And nothing could be more true than in the area of artificial intelligence. There are many groups when they hear AI, it actually raises more of a sense of fear, particularly in the healthcare domain. Can we trust this? It’s a black box. We won’t understand it. The BCRF support of myself, of Regina Barzilay, of Adam Yala, really they’re standing by their commitment to push the field forward for a paradigm shift. I’m so excited about it because in my entire career as a breast imager, I’ve seen the limitations of how we screen. We had screening mammography in the late 1960s in the US. Not a lot has changed.

We’re still making recommendations for how women should be screened mainly based on their age and breast density when we have so much data about women where we could be more precise, more effective, and save more lives. We also have a lot of work to do in early detection, to have it more equitable and to have not only access more equitable, but also the outcomes. It’s not just about people being engaged, but about reaching the right people with the right tests at the right time. So probably 25 years ago, I was studying my grandmother’s CAD, old school cad. That was machine learning. And you may all have had mammograms where you know that it was interpreted with CAD, an older technology of-

Dr. Norton: Explain what CAD is.

Dr. Constance D. Lehman: Machine learning. Computer-aided detection or computer-aided diagnosis. So computers assisting radiologists isn’t new. We’ve been working on this area going back to the 70s and 80s.

The FDA approved the first CAD product to interpret mammograms in 1998, but we found with the Breast Cancer Surveillance Consortium that it wasn’t translating to improved mammographic interpretations. And that was a hard lesson, but one we’ve carried forward to today as we’re now studying the next level of computer data detection about that. So we’re now going from CAD to deep learning. And what was probably one of the more exciting times in the field was around 2010 or so when computer vision really started to show promise in being able to use neural networks so that computers could separate out different types of images.

So then we realized all of the images in healthcare, whether it’s a lesion on the skin, an image of the body, an MRI, an ultrasound, a CT, a mammogram, the back of your retina, all of these images we can use with these big databases to train AI models, machine learning and deep learning models to be able to read these images independently, either to assist the physician or in some domains we are going to have examples where we can replace the physician. I think what I became most excited about when I first met with Regina Barzilay and we started talking about the potential of this was to leverage AI to do things that humans are not doing. We’re not terrible at finding present cancers on a mammogram, but we could certainly do better. But what we can’t do is look at a mammogram and judge a woman’s future risk of breast cancer, but we can with AI.

So that is the area that’s particularly exciting and where our work comes together. If we want to have prevention methods, wouldn’t it be great if we had a tool that could assess if that intervention is decreasing a woman’s risk? Many of my friends that have gone through breast cancer and are then put on risk-reduction strategies, and I find out after a few years that they just don’t stay engaged. There’s other side effects or problems, but I really believe that if they saw the impact it was having on their risk, it would give them an incentive. And if it wasn’t having an impact on their risk as assessed by the AI mammogram, to shift to a different type of intervention. Whether we’re working in obesity or hypertension or diabetes, we can give patients feedback about the interventions and how they’re influencing their risk. I think in the future, we’re going to do that with breast cancer as well and it really opens up so many different areas.

The last thing I’ll say before passing on to Seema is what was very exciting as Regina and Adam Yala and I were studying the outcomes of these tools in our clinical populations, we’re seeing that there is equity across diverse populations. We haven’t had that with our other risk tools, and we’re very excited about that possibility to provide accessible, affordable, and equitable care to more women in assessing their risk, intervening early, and preventing cancer. So thank you for your support, and I look forward to our questions and answer.

Dr. Seema Khan: Thank you, Connie. So I too would like to thank BCRF and all the support that they have provided to myself and other researchers like me who are focused on breast cancer prevention mainly. But the avenue to effective prevention is actually identifying women who are at risk for breast cancer and estimating that risk. So a lot of what I’m going to say is going to relate to what Connie Lehman has just told you, but I’m a breast surgeon at Northwestern University in Chicago, and I’ve been interested in breast cancer risk and prevention since early in my career. If you remember, this whole field was actually started by a surgeon. So a good role model, Dr. Bernie Fisher led the first prevention trial testing the value of tamoxifen for risk reduction, and this was published in the late 1990s.

There was a lot of excitement at the time because tamoxifen appeared to reduce the risk of breast cancer in women at increased risk by 50 percent, so halving the risk of breast cancer, and there was real anticipation that this intervention would make a difference in the occurrence of breast cancer and help women who were at increased risk. Unfortunately, over the next decade or so, we realized that what was anticipated to be a safe and tolerable intervention treatment for high-risk women turned out to be not so tolerable. And it was not perceived as safe enough for high-risk women to use when they were healthy if breast cancer hadn’t happened yet. So since then, over the past decade, I think there’s been a lot of attention paid to this question of how we can take an effective medication and reduce the risk of toxicity and increase the tolerance so that women who would benefit from such intervention would accept it.

There are many people who worked on this. Dr. Jack Cuzick is here, Dr. Andrea De Censi, and people from my institution. We’ve all been approaching it from different directions. The tech that we chose initially was to try to develop a gel formulation that would be applied to the skin of the breast, would concentrate in the breast, but have very low circulating levels. So this would deliver the benefit of the medication to the breast, but would avoid side effects. So with BCRF support, we were able to work on this for some time. This is a process in development at the moment. The initial data are encouraging, but more work needs to be done. And again, we really appreciate the support of the BCRF and of all the BCRF supporters as well.

The newer tech is low-dose tamoxifen, and that is something that we are pursuing in the next phase of work based on trials done by Dr. De Censi. So we think of this as a renaissance in tamoxifen use and in medical prevention, because obviously the alternative is surgical prevention, which is effective, but is also a big burden for women who are considering it. So we have to strike the right balance and offer the right intervention to women who need it.

Dr. Norton: Thank you. I would just say that it is such a shift in the kinds of discussions that we’ve had here in front of you, I don’t know how many years we’ve been doing this, but a whole lot of years in terms of contact, from some of the issues that we were discussing back in the beginning to where we are now. If you just think how remarkable it is, we have among our panelists, an expert in genetic in things you inherited from your mother or your father that may give you risk, ancestry in terms of geographical ancestry, social determinants of cancer, and an expert in breast imaging.

We always think of breast imaging as you find a cancer so you can go and take care of it. But now we’re getting into the area of actually looking at a breast that is normal and saying, “Gee, this is at higher risk,” and we have to take into account social determinants and geographical ancestry andusing the most modern tool that we have in analyzing complex data sets, which is artificial intelligence and machine learning. And an expert, a surgeon who’s trying to put herself out of business by preventing breast cancer in the first place. So she has nothing to operate on. And then she and I are going to open a bakery together. That’s our ultimate plan.

And this is a prevention strategy that is so benign that everybody could take advantage of it and without fear of side effects. So we’re talking about identifying people at high risk, we’re talking about not only detecting cancer, but finding by a mammographic image the probability of developing cancer and intervention strategies. It was inconceivable when we started this that we’d be talking about prevention to this degree and in this way, and especially with these advanced tools that we’re talking about. Aa\nd genetic analysis is very complicated, very detailed, very hard to do. Obviously mammograms have so much information in it that you need computers to help you interpret it, and pharmacological advances, advances in medicinal chemistry that allow us to deliver these drugs. I’m just blown away by this. We also have another expert here happens to be in genetics, and I’m going to pass the baton over to Judy to have further discussion on this topic.

Dr. Garber: Well thanks, Larry. And I have to say Funmi has been a colleague on the genetics journey all my career. And there are many others in this room who are expert. But I think genetics fits in. If we’re thinking about how do we find women at highest risk, some of them have genetic risk, some of them have no family history, no genetic risk, they get breast cancer anyway. Are there subtle genes that are still less powerful but able to help us identify who’s at risk? And we could say if we could figure out who is at risk, however we do it, we might be able to have a much more efficient system.

Connie talks about risk-based mammographic screening, so we wouldn’t all have to go sign up at 40 or 50, depending where you live, every year, every other year. If we had more sophisticated risk estimation, we could stratify who needs to be screened frequently or less frequently, like we do for colonoscopy. And if Seema is able to give us really effective, acceptable prevention strategies and we work on those things too, then great. We wouldn’t all be as afraid of this as we are. And then we could come back to Funmi and ask Funmi, you covered so many things, you’ve had so many interests in your time. Where do you think are our greatest opportunities for moving forward now? Thinking the way you do so broadly, so globally, how can we make the biggest difference?

Dr. Olopade: Yes, thanks Judy. When we started really mapping genes one gene at a time, we had a promise that we can map the entire human genome. And I remember when we got the good news that Congress was going to give us $5 billion dollars to map the human genome. And it was a bipartisan congress that gave us $5 billion. It seemed like a lot of money. And we talk about the fact that it took $1 billion and $5 billion to find the first map of the human genome, and now we can actually do it for less than a thousand dollars. How powerful is that? And Larry’s always talked about mathematics because he’s a genius. He thinks mathematically.

Dr. Norton: It’s true. It’s totally true.

Dr. Olopade: And we had at our symposium yesterday a talk about mathematics in medicine. Who would’ve thought? If I knew mathematics was going to come back to medicine, maybe I wouldn’t have been a doctor. Because what you need is data, and you need technology. And some of us are concerned about data, about whether the internet and people are fixated on social media, and that’s bad for us. But there’s technology for public good. And one of the amazing things that we are doing now is getting data from all over the world. Women get breast cancer in every country and in every neighborhood, and we can actually map where the worst survivorship for breast cancer is in this country because from 1975 till now we’ve been recording cancer as a reportable disease. It’s the only disease that you actually must report from every hospital. So imagine if we can pinpoint where the most vulnerable patients are.

And by the way, my husband is in the audience, and he tells me we don’t need to do breast cancer research. We only need to fix the environment. And so between the environment and genetics, we have this tension in my family because I think we have a foundation. We’re born with the genes we’re born with and then life happens. So what are those lifestyle trajectories that we can actually intercept? So I’m very excited at this moment that we are finally having the tools to pull all of it together so that we can do cancer interception. We cannot wait until people walk into our door with advanced cancer to treat them. We can monitor them, we can check them, we can tell them to exercise.

I ran the marathon last year. Why? Because everybody told me I have to increase my metabolism. I shouldn’t gain weight after menopause. Those are all important things to help us change our lifestyle. So I’m very optimistic that it’s not whether we do this or that. It’s like we’ve all to come together in solidarity to use the evidence we have now and keep building on it. And luckily we have young men like Dr. Yala, who as a graduate student working with Connie at MIT, was thinking about women with breast cancer and about developing tools that those of us who never knew mathematics can actually press the button and then it gives us the answer. How amazing is that?

Dr. Larry Norton: Connie? Do you think AI is going to help sort out all of the complexity of the data that Funmi is talking about?

Dr. Lehman: I think it’s certainly going to be huge. It’s so fortuitous that at the same time, we had diagnostic methods that were collecting more and more volumes of data, whether it’s genomics or radiomics, the imaging data, at the same time we were having computers have such increased speed to be able to process and manage that data. Many of us in healthcare were worried that we were getting so much more data out of our patients that we could possibly process. And that’s where I think AI is really going to influence every domain of breast cancer.

Dr. Norton: You said something that sent a chill down my spine, is maybe we can eliminate doctors, Connie. That’s a terrifying thought for many of us in the room. No, I’m just joking. Actually, I am impressed even to this day by how much information I can get while I’m talking to a patient just by taking my smartphone out and asking a question and getting some further information in that regard. So this interface I think is one of the really important areas. You have a comment on that?

Dr. Lehman: Absolutely. And I am so grateful. Many of you in the audience are also helping spread the word of these paradigms that are shifting. So depending on our age, we’re either extremely comfortable with computers being a part of our lives, how we feel about a self-driving car, whatever our experiences are, AI is permeating so many different facets of our life. It can be a little bit fear inducing to think about it in your healthcare. Many of my patients will say, “I trust you as my doctor. How can I trust a computer?” But that’s where we in the medical environment are going to be educating ourselves and educating others on how this is really enhancing our jobs.

My friends that are breast imagers, we cannot wait until we can take some of the tasks that we do that we know computers can do better and offload those onto the computer so we have more time to spend with our patients, to provide greater access, to be much more refined in our conversations and discussions about the best personalized screening strategy, the best personalized diagnostic pathway for the patient in front of us. So hematologists aren’t looking under a microscope counting red blood cells anymore. We pass that off to computers. There are a lot of domains where it was a change, but we were all very excited about that transition.

And the same will happen with interpreting images. We have the FDA involved because the regulatory process is extremely important in AI. The FDA has already approved a new domain for AI, which is triage to take exams, whether it’s a scan of the brain looking for a stroke or early signs of a stroke or a mammogram, to scan them and say, “This really doesn’t have anything remarkable. Let’s put this at the bottom of the list. These others need extra attention.” So we’re already seeing the FDA engage in this process to move the field forward, and we’re going to continue to see that trend.

Dr. Norton: How is this influencing cancer surgery? What are the changes that we’re seeing in approaches to cancer surgery that are happening with this data revolution and other things that we’ve been talking about?

Dr. Khan: Well, surgery, as we all know, is the oldest treatment for cancer. So it has stood the test of time and it is an integral part of cancer treatment today and will remain so for some time, I believe. The way that AI advances are influencing cancer surgery will probably not be totally apparent for some time. I think where the information that Connie is talking about does influence us is in risk estimation. So again, as I’ve said, surgeons are very interested in preventing cancer as well.

And so many of us counsel high-risk women about interventions, and it’s a partnership between the breast imagers and the breast surgeons counseling women about the appropriate imaging strategy for them. And that’s where AI is likely to make a difference in the near future. The longer-term effect on cancer surgery might have to do with predicting a response to neoadjuvant therapy, for instance, which is increasingly used, as you probably know. Somewhere around half of women are now being considered for medical treatment prior-

Dr. Norton: That’s using drugs before we operate to shrink the tumor down and make it disappear.

Dr. Khan: Right. Medical treatment prior to surgery to try to shrink the tumor and get some information about the effectiveness of the medical treatment, the chemotherapy for that particular tumor in that particular woman. So that information is very useful both in planning surgery and also in planning downstream medical therapy. And that’s where these kinds of algorithms may fit in to help the surgeon decide on the appropriate surgical recommendation. But at the moment, it’s in detection and risk estimation that AI is having the biggest impact, I think.

Dr. Norton: Very good.

Dr. Garber: So Larry, I’m going to take what could be the last AI question. We may have to cover some other things, but this is really for you. How do you see the future of clinical trials? How can AI better inform drug discovery?

Dr. Norton: Well, there’s two questions there. The future clinical trials and the question of AI going forward in that regard. Clinical trials are absolutely essential. I differ from a lot of my colleagues in one important respect. I still think strongly that randomized clinical trials going forward are the way that we get clear answers, and that’s when somebody who’s a candidate for the trial can get one treatment or the other or can get standard therapy versus other therapy rather than just trying something and seeing how it works and comparing it to historical experience. But that is happening as well. And we can debate it and we can argue it. I think that the big transformation that has to occur is that we have to democratize the clinical trial process. We have to get clinical trials out for everybody, certainly in the United States, maybe even the world, that has a certain disease that’s a candidate for the clinical trial and bring the clinical trial to them.

One of the really painful things that I have to deal with all the time is getting phone calls from somebody who  has advanced disease, metastatic disease, that has the potential of being helped by an experimental drug that is coming down the pipe that looks very promising., And we may even have early evidence that the drug works but we’re not be able to get that drug to them because they don’t have access to the clinical trials where the drug could be provided by geography or by economics or by inclination because of past experiences for themselves or their family or even their cultural group. So I think that one of the major things that we have to do is we have to make clinical trials available for everybody. And I think that’s really one of the most important things that we have to address. All right, and that’s the last question I hope I’m going to have to answer.

Dr. Garber: You’re not going to do the AI question?

Dr. Olopade: Actually I can maybe help my colleague because there’s something that’s actually fascinating with AI in every area of our life, and I’ll give you the example of what happened to me this summer. We had students in the college coming to do experiments in the lab. And because we have mapped all the genes, all the proteins, and we know how the proteins are configured, and you can just go to the computer and say, “If this mutation occurs in a breast cancer cell, how can we drug it?” And these literally third-year college kids came back and said, “This is where we can drug this because the protein is being mapped.”

So AI will influence how we even begin to test which drug we should go after. And there are lots of ways in which we do chemical screening—there’s what is called now chemical biology, computer biology, so that we are all looking at a way to accelerate and make things happen faster. Some of the work that BCRF has funded is I-SPY, where we want to get a biomarker to the right patient at the right time. And lastly, you take wedding photographs using drones. Imagine if we can deliver drugs to somebody’s doorstep with a drone. It’s going to happen.

Dr. Norton: Connie?

Dr. Lehman: I love your out-of-the box thinking. And also I think in the specific domain of drug development, we’ve seen some examples in the past where drugs—especially those designed to prevent a cancer occurrence—where it’s been very difficult to do those trials and wait to see who gets cancer and who doesn’t get cancer. So some groups have said, “Well, could we impact the breast density? Could we look at surrogate markers of risk?” And those have shown some interesting results. But AI on the mammogram, if it’s showing us risk and it’s showing modifiable risk factors that will change that risk on the mammogram, you could have an earlier indicator of promise in certain drugs versus others.

The second domain is we know, and it’s so frustrating when you see drug trials where it helped some women so much and didn’t help others. In the domain of precision medicine, can AI help us identify those that will benefit from that drug and move out the subgroups? The same thing with mammography. Mammography is a great tool for a lot of women, and it’s a really poor tool for others. Can we start to be more precise because of the AI power to help us categorize women more effectively and look for changes in risk with different drug trials and interventions?

Dr. Norton: Seema?

Dr. Khan: So yes, I just want to add that what Connie has been mentioning is actually going to be tested in our BCRF-supported clinical trial that will begin soon, hopefully in a few months, where we’ll be starting premenopausal women on low-dose tamoxifen five milligrams a day based on Dr. De Censi’s work, and then testing their response in terms of breast density. So breast density is known to be reduced in many women by the use of tamoxifen, and we will be following their tamoxifen response using breast density and also assessing their risk reduction with the AI tools that we’ve been talking about. So this new generation of trials will be putting these concepts into practice, at least at the level of clinical trial testing.

Dr. Norton: Yes, I can’t help but jump in with a couple thoughts in this regard. The thing that really is impressive about AI is that the way science has been done in large data sets—the way science has been done for centuries—is you have to have a hypothesis. You have to have an idea, and then you have to design an experiment to test that idea. By looking at a tremendous amount of information now using these modern electronic tools, the idea can come from the data rather than having the idea first and then looking for data to support the idea.

Look how many centuries it took us to figure out that cigarette smoking caused lung cancer. It would take an AI tool a few milliseconds to make that observation, People do a lot of things, of which smoking is only one of the thousand things that people do, and if you actually had the data, it would find it instantaneously and then you could also test it going forward. The other point I want to make is yes, I’m a mathematician, and we have other mathematicians researchers that are all arrayed around you in this regard. I think the interface between machine learning and AI and mathematics still is an area of great potential of development. AI is a tool for looking at large data and finding patterns and discerning them.

I’m reminded of the analogy I always use in this regard, which is that you can look at the night sky forever and collect all the data about the stars, but actually making sense of the motions of the planetary bodies can only happen when you have a mathematical hypothesis, which is the theory of universal gravitation and the mathematics of calculus, then it all makes sense. But you can’t develop calculus and the theory of universal gravitation unless you have the data and unless you’re able to analyze the data. And that’s why it took so many centuries to actually figure this thing out.

Had we had computers at the time of Kepler, for example, Copernicus, it all would’ve sorted out extremely quickly because you could test a lot of ideas about the way the planets interact very, very quickly by looking at the data. So we really are in a different world. This is one of those quantum leaps, I think, of human intelligence where the data itself can generate the hypotheses that we can look at, and where it’s all going to lead is really exciting—alittle frightening but actually profoundly exciting moving forward. We have a question from the audience there.

Dr. Garber: We do, and I would just add one thing, which is that AI is a fabulous tool, but as everyone said, it’s a tool. It has to help us be smarter and we’ll still need clinical trials to prove that what we think is the right tool is actually predicting correctly and that the ways that we modify actually work. So I don’t think we’re finished yet.

Okay, so we’ll shift gears a little bit. Here’s a question, maybe Seema, you might want to start this one, which is about breast cancer in men. So breast cancer in men is a little better understood than before. We’re recognizing that breast cancer in men certainly happens. We’ve known that. What are we learning from women that might inform our ability to take care of men?

Dr. Khan: Breast cancer in men, of course, happens much more rarely. It’s about 1 percent of the rate that breast cancer happens in women. But we have learned over the past decade or more that there are some genetic susceptibilities that increase the risk of breast cancer in men, BRCA2 being the most prominent, but also some others including BRCA1. And so the one thing we’ve learned when we see a man with breast cancer is that this is an indication for testing of that man as well as his family members if his cancer proves to be related to a genetic inherited mutation. And then those men are also at increased risk for prostate cancer. So that sets in place the whole sequence of other considerations that apply to people with genetic susceptibility.

In terms of the actual treatment of breast cancer in men, it seems to be fairly frequently hormone sensitive that is responding to anti-estrogen medications, and those are used regularly in men. The surgical treatment is mainly similar to that of women. Typically in a man’s breast, a breast cancer occupies enough space and there isn’t enough breast tissue to really think about breast conservation. So most men with breast cancer are treated with mastectomy, and then the follow-up treatment is really based on the characteristics of the tumor. But again, many times endocrine therapy, anti-estrogen therapy is very effective. One other issue about breast cancer in a man, the risk is increased after hematologic malignancies. So the data from the surveillance and results reporting from the big database that’s maintained by the NCI suggests that breast cancer as second malignancies is also more frequent in men.

Dr. Norton: Do you have other thoughts to add to that?

Dr. Olopade: Well, she’s covered everything.

Dr. Norton: All right. A question for you, Connie. We’ve been talking about mammograms. What about MRIs? People out there are being recommended to get MRIs. Some of them are getting an MRI every year, some of them are getting mammograms every year, but other countries recommend mammograms less frequently than that. What are your thoughts about that and how it relates to your work?

Dr. Lehman: We have so much good data that tells us one thing. If we want to find more cancers above and beyond what we can see on mammography, we need to do vascular imaging. I’m not saying contrast-enhanced MRI, I’m saying vascular imaging. Contrast-enhanced mammography—which BCRF is supporting via a fabulous trial with Chris Comstock and GE and the American College of Radiology—appears to have the same power of contrast-enhanced MRI, but at a fraction of the cost, and it’s globally accessible. If you have a modern mammography unit, you can upgrade that mammography unit and then inject a contrast agent and get the same power that you get from MRI. So I’m a huge proponent, huge fan of vascular imaging, and I hope in my lifetime we shift from MRI to contrast-enhanced mammography, as the globally accessible, very powerful way to find cancers that are hidden on a regular mammogram.

Dr. Khan: Hear, hear.

Dr. Garber: Amen.

Dr. Olopade: Maybe I can offer another example of why we’re talking about precision. When you have a problem, you want to make sure that we are working on the best tools to actually find that cancer. I talked to a lot of physicists and they’re telling us now that we can actually find the smallest molecules that are becoming deranged to cause cancer. So it’s not just about imaging to find cancer early. Yesterday we heard about early detection, multi-cancer analytes, things that are shared by the earliest signs of cancer that we can get from a blood test. Now when I say it’s coming, the same thing about the human genome, we thought it would never cost a thousand dollars. Phones will never cost a fraction, but the science keeps getting better. And what we want is what’s going to work. In the meantime, we did an experiment with Dr. Comstock in Chicago when he was younger.

What Dr. Comstock wanted to do at that time was to have me get my patients with BRCA1 mutation who will get breast cancer at the age of 30 . There’s no recommendation for how you find cancer in a 30-year-old or a 25-year-old. And that technology has matured to the point that those women will come to us now and they can get an MRI, they can get it faster, cheaper than when we first started, that in four minutes we can actually image their breasts. So these women can have babies, can do whatever they want, and at the time that they’re done having their children, they can make a decision whether they want to have surgery, go to my friend to go and have their breast off, or just keep screening. That experiment started in 2004, and guess what? We’re no longer in 2004, we’ve gotten it faster, and cheaper because the technology allows us to reassure these young women that “Yes, you were born with a BRCA1 mutation, but come to us, we’ll take care of you.”

And what we learned by doing that study was their anxiety level went way down. They had their babies, they breastfed their babies, and they’re going on with their lives. That’s the power of integrating science and technology so that every woman has a chance to get the right treatment at the right time for the right disease. And so for us, we’re now testing this study nationally, and that’s what WISDOM study is about. Let’s find the highes- risk women. Have you all done your risk assessment? I’ve done mine because one size doesn’t fit all. I want to know, it’s a bell curve, am I on the extreme of risk or am I on the extreme of I don’t have any risk, or am I a little to the right? And I happen to be a little to the right, so I’m going to do something to reduce my risk.

That’s what precision prevention is about, and it gives us an opportunity to lower risk and catch cancer early. So we continue to do the research because we don’t know what’s going to be better in the future. And that’s why BCRF brings us together and we can test a lot of different ideas so we can finally begin to think about how to get it right for every woman. Because right now we don’t know enough on who’s going to get cancer and when they’re going to get cancer. And if we can make sure that they never die prematurely from breast cancer. That’s the goal.

Dr. Norton: That’s where we’re at. Dr. Comstock, are you here? Tell them about BCRF’s supported study.

Dr. Christopher Comstock: Larry refers patients, and he sees the power, as Connie mentioned, in vascular-based screening. And our biggest, I think our quickest, fix to lowering mortality because too many women still die of breast cancer each year is that mammographic. Our current gold standard of 3D mammography is maybe 30 percent sensitive. And so we have twice as many cancers walk out the door that we find after looking through all those images, and vascular-based screening can significantly, by two and a half fold, increase our sensitivity. As Connie mentioned, it’s very accessible and it can be done on most systems throughout the country by just a modification and then giving contrast. So it’s vascular-based screening and it’s not affected by breast density. So that’s the problem with mammographic screening. The more dense breast tissue, the harder it is to find cancer.

And these tools, MRI and contrast mammography, overcome that limitation, reducing sensitivity. So with BCRF, along with GE and the ACR, we’ve just launched our trial at four sites. We hope to have 10 sites up and running soon. The trial is looking at contrast mammography as a new paradigm for women to have screening if they have dense breast tissue. We couldn’t have done this without Larry and BCRF. As Connie mentioned, I have a slide of pictures of different aspects of society from mobile phones to computers. And in the 50s, when mammographic screening started, a 5MB hard drive was two and a half tons, a massive piece of equipment, and now it’s a little card in your phone that holds a terabyte.

But mammographic screening is just improved slightly with, we went from analog to digital, added tomosynthesis. I call it the art car phenomenon. On the West Coast, San Francisco, you see these pictures of cars where they’ve glued on all these different ornaments and statues and they’ve made it fancy. But the problem is that’s mammography. It’s this art car phenomenon where we’ve added all these little increments but we haven’t compared them to the rest of society. And now with AI, we’ve got a whole other model of doing screening, and hopefully with this trial BCRF will usher that in.

Dr. Norton: Thank you.

Dr. Garber: I was just going to point out that we hear all of this. It’s so exciting, it’s so promising, but you have to prove it. Before you have the country decide that we’re going to invest in upgrading all of our mammography machines, we have to prove they work. That’s why there’s research. That’s why there are trials, because of course we’re all excited about things that sound new, but we have to do the rigorous work to prove that they’re better before we change practice in the world.

Dr. Lehman: And we’ve learned again and again and again that where we had the excitement, the enthusiasm, the ideas, the creativity, rigorous scientific trials showed us we needed to go in a different direction.

Dr. Norton: You asked me the question before is a well-designed clinical trial, whatever the outcome is, is going to be important information going forward. And so that’s the art of clinical trial design, which we have many people here that do it moving forward. Judy?

Dr. Garber: So I have a great question, but it’s also for somebody not on the stage. Dr. Finn, would you speak to research being done on breast cancer vaccines? Dr. Olivera Finn is at the University of Pittsburgh, and she has spent her career in immunology working on vaccines in colon cancer, but we’ve enticed her to work on breast cancer.

Dr. Olivera Finn: Thank you very much, Judy, and thank you for the question. This is my very first BCRF event, because I’m your new grantee, but I’m really excited. It’s also the 30th anniversary event, because exactly 30 years ago, in 1993 December, I started the very first clinical trial in a cancer vaccine in patients with advanced colon, pancreatic, and breast cancer. And my very first patient was a breast cancer patient who was basically dying of breast cancer and she signed up for the vaccine and she told me, “I know this is not going to do anything for me, but I really don’t want anybody to live through this through what I’ve just lived through.”

So the same vaccine with slight tweaks is now what BCRF is funding for breast cancer prevention. And we have spent 30 years showing that it is safe, that it can be effective and more effective if the woman is not suffering from advanced cancer because we have learned that in the setting of advanced tumor, not only our vaccine but all cancer vaccines—and there have been many tested in clinical trials—are very strongly impaired and compromised in their effectiveness by the immune suppressive environment of the cancer. So it is much better if we can use them early. And you know, vaccines have saved the world many times before against infectious disease. The latest example is our COVID-19 vaccine.

So the same way we are preventing infectious disease, we are going to prevent cancer. And we are doing this in baby steps because as Judy pointed out, we have to prove that this works. And the baby steps are not taking a seven-year-old and giving her a vaccine or a 15-year-old girl and giving her a vaccine, but taking women at very high risk, however we define the risk, and we had the whole discussion on that. So, we have to work on this together. Right now, what we are doing for my trial, our trial in Pittsburgh as well as several trials going on all around the country, one at the University of Pennsylvania for the BRCA 1 and 2 mutations, is to diagnose pre-malignant disease. Judy mentioned our colon cancer work. We actually vaccinated people with a history of advanced polyps that are immediate precursors to colon cancer. And those polyps are removed via colonoscopy, but over 60 percent of people who have those polyps can recur with other polyps one to three years later. So, we vaccinated right after the polyp removal, and then we observed for five years, and in people who responded well to the vaccine (because even at that level there’s some level of suppression at that stage), there’s some level of suppression, but we had a lot of responders. Those who were vaccinated had a 38 percent reduction in polyp recurrence and (are still polyp-free). Which means that there is a 38 percent reduction in your risk of developing new polyps that can progress to colon cancer.

The breast cancer equivalent here now in what we are trying to do is women with DCIS, ductal carcinoma in situ. You all know that is not a cancer. However, we don’t know what the risk for the woman with DCIS is for progressing to cancer, so it’s surgically removed, otherwise other times differently treated. We are going to vaccinate women newly diagnosed with DCIS with our vaccine. The vaccine is expressed on all breast tumors and on DCIS, and we are going to measure their ability to respond to generate a very strong immune response. And then the women will have standard of care—those who want surgery will have surgery and we will have tissue to compare the initial biopsy with the tissue post-vaccination.

If we see that we have one, induced a very strong immune response to our vaccine and two, that we have brought all the immune cells to the site of DCIS before it was taken out, we might in the next phase of our trial just wait because the immune system should have the capacity to get rid of that lesion without having surgery. And it should also protect the woman in the future from developing new lesions. As you know, that can happen in the other breast, et cetera. So, we are very excited about that. Similarly, in the study at Penn, they are using a very similar vaccine but in carriers in BRCA 1 and 2 carriers. Would you like to comment on that?

Dr. Laura Esserman: Yes, I’m presenting at San Diego at AACR on Saturday. We have been doing a phase one study using a Moderna mRNA with a cocktail. I’ve been working on this for several years. BCRF actually funded a lot of the work that led to this. So if you directly inject into the DCIS and let the DCIS be its own vaccine so you can organize it, you can bring the immune system cells in great numbers. Now most DCIS are slow-growing and hormone-driven. They’re not immune-driven, but there’s about 10 to 20 percent that are, and they can be these very big lesions, but we used to think those were the worst DCIS. But you have to ask how is the body already containing them? And it’s probably the immune system that’s keeping them intact. So we now have, when we combine pembrolizumab ( Keytruda), one of the drugs that takes the brakes off the immune system.

But again, you don’t want to give it to the whole body when someone’s got pre-cancer. You want to just give it locally. And then we added this mRNA cocktail to our 10 patients. Eight of the 10 patients had the big immune cells in their DCIS already. And all of them responded. Four of them went away completely, and three of those patients have not had surgery and they’re now over a year out without anything left. I think we’ve already shown that this is possible now and we’re expanding it. And it’s another way of saying we don’t have to know. It’s as if you were injecting the polyp right there, we can inject the DCIS right there and have it go away.

For the hormone-driven DCIS, we’ve also shown that if you give endocrine risk-reducing agents, these are the people who are the most at risk for ER-positive disease that maybe 60, 70 percent of people will never progress. And we of course use MRI as a way to measure this and to really look at who’s got endocrine-sensitive and endocrine-insensitive disease. We’re starting a study across the country called RECAST where we are testing new endocrine types of agents, testosterone, looking at endoxifen, which is the active agent for tamoxifen.

Dr. Norton: I have to ask this question and the right person to ask this is Dorraya El-Ashry, the chief scientific officer from BCRF. One of the things we’re hearing about here is the interactive-ness of the various scientists and the various collaborators that we have. Once we start on a topic, essentially anybody could stand up and talk about how they’re related to this topic. Do you have data on how interactive we are as an organization?

Dr. Olivera Finn: Larry, I’ll just add that everybody who I talked to at this meeting about our trial asked how many patients are involvedand can they also contribute? So that’s the other thing, that all BCRF investigators here who, including Seema, I was sitting next to her last night, said, “If you have slow accrual, get in touch with us.” Beth Mittendorf offered. So this is a community that immediately can form these sorts of-

Dr. Garber: Interactions.

Dr. Norton: Absolutely.

Dr. Garber: Thank you.

Dr. Laura Esserman: And Larry, I just wanted to say, the WISDOM study. Anyone here who hasn’t had cancer can participate.

Dr. Garber: One more take.

Dr. Laura Esserman: Wisdomstudy.org. Thank you. Dorraya?

Dr. Dorraya El-Ashry: Good morning, everyone. You’ve been hearing about the most impactful and tremendous progress that is being made in the fields of disparities and prevention this morning. But what I also hope you’ve heard, and what Larry mentioned, is how much of this is being done in a collaborative way, and that this is the future of taking great ideas forward. And BCRF has had as its hallmark fostering collaboration. In fact, as we do our five-year impact reviews and reports, we pull together this data on collaborations of BCRF investigators, both with other BCRF investigators that are fostered at events we hold, like the research retreat we had yesterday as well as at many think tanks as well as with outside investigators, which only extends the impact and reach of BCRF funding.

From a cohort that we have looked at and from each of these years, BCRF investigators collaborate on average with three other BCRF investigators and with clinical trial groups that we support at a tremendous rate, and at a rate of five to six times non-BCRF investigators. And so the amount of collaboration that is both fostered by BCRF, but also because all of these investigators know that the way we move things forward is through team science, has just been tremendous.

Dr. Garber: Funmi, there are some communities that have a very high incidence of young, advanced disease women with metastatic breast cancer. Are there environmental factors or social factors that you think might contribute to this particular problem?

Dr. Olopade: Yes, thank you for asking that question, and I hope some of the epidemiologists in the audience—and there are many of them here—would chime in. When I started my introduction, I talked about the south side of Chicago. One of the areas that we’ve really been focused on is environmental justice. Dumps and every toxic chemical is put in poor neighborhoods. And we have been very concerned about not just environmental pollution that you see outdoors, but household air pollution. About three million women and children die globally from household air pollution because they burn dirty fuels.

Just this morning we were talking about the PM 2.4, particulate matters that we may think don’t matter. We’ve spent a lot of our time looking for genetics. What are the genetic causes of breast cancer? And we’re now actually also funded by BCRF to look at the epigenetics. As we are all sitting here, mutations occur. Most of us have the immune system to wipe away the mutations, but somehow some mutations cause derangement of other genes, and you have this cascade going on that then leads to advanced metastatic breast cancer. Globally, the fastest-growing breast cancer community are premenopausal women. It’s become an epidemic, and the World Health Organization has actually put in a call to say, “Why are young women everywhere getting breast cancer before the age of 50?” What’s in the environment? What’s in our lifestyle? My mother had six children and breastfed for 21 years. Who does that anymore?

Dr. Garber: More recovery.

Dr. Olopade: Right. So, it’s a women’s health issue because we don’t know what’s happening to the modern woman and what’s happening to our environment, and I think this is where we need political action to have more support for women in the workforce, more support to diagnose cancer if you’re going to get it before the age of 50. And of course, to always really think about environmental justice, because it is true that when we map the areas with the most disparity, where people are most likely to die from breast cancer, it’s also the communities that are most affected by environmental injustice. And we all have to really do something about that.

Dr. Norton: Yes. Connie, you’ve done some fantastic work on differences—I call it geographical ancestry— in terms of AI and risk prediction using your models. Do you want to talk about that a little bit and then maybe answer the question that I handed to you?

Dr. Lehman: Sure. So many of us have heard of the domains with AI where errors were made because the trials used predominantly light-skinned patients. So for example, some of the dermatology AI tools cannot accurately diagnose disease in people with dark skin, and that was extremely concerning because we have a long, long history of racially biased research and clinical care around the world. We were delighted to find with the AI applied to interpreting the mammogram for a future breast cancer event, that it was equitable across races. We studied this carefully at Mass General, populations across Hispanic, Asian, African American, and Caucasian, and in other domains in other centers as well. So I think one of the reasons is because the model can learn from the image itself how all these differences are being expressed and displayed, whether it is the endocrine challenges that a woman has gone through during her life or different factors and features of race, et cetera.

So we were very enthusiastic about that, but think it is imperative, as Judy points out, that we continue to rigorously test. We now have, and this gets to one of the questions that I was asked here, “Well, is this available?” Right now there are about four or five different risk assessment AI-type tools that are being used. The FDA has made it very clear that these will need to be regulated by the FDA, so that’s a murky area right now. Vignesh Arasu at Kaiser studied and presented with a single database with known five-year outcome of cancer outcomes in a cohort of patient— both the clinical Breast Cancer Surveillance Consortium, a clinical risk assessment method that is more traditional of how many family members have breast cancer, how many children did you have, did you breastfeed, et cetera—and compared that to these different AI tools. He found that the AI tools that have been developed at multiple different centers, including NYU, including some different companies, performed significantly better than the clinical approach.

That study was fantastic because it also uncovered that some of these tools are actually finding cancers that are probably present at the time on the mammogram and the computer vision is identifying it, but it was missed by the radiologist that was reading the exam. So that’s why the clinical research is so important. We’re still early in understanding how this is working. The question was also are there prospective trials of MRI? This is a tricky area. The direct answer is there is not a prospective trial seeing the impact of MRI in clinic, that would take a minimum of five years if we wanted to see the prediction of a future breast cancer. And these models are evolving rapidly, so that’s a little challenging. What we’re doing in our very large Mass General cohort is looking to see how did MRI distinguish from those women that were undergoing screening with a high cancer burden and a lower cancer burden.

We can use registry data for that. We have done that and shown that we are better at identifying patients with cancer who undergo screening MRI, and we can identify those patients that probably didn’t benefit at all from the MRI. The same with more intensive mammographic screening and less intensive mammographic screening. We look to our mathematicians, our epidemiologists, our biostatisticians, for creative ways to develop and evaluate these risk prediction tools to try to set prospective trials with five or six years needed to see what the impact is as they’re developing so rapidly, and it’s going to be challenging.

Dr. Norton: Excellent, thank you. There was a lot of interest out there and I got a lot of questions about this, is the idea of getting tamoxifen out as a prevention strategy. What are the toxicities of tamoxifen that you’re trying to reduce by your methods?

Dr. Khan: What we know about the toxicity of tamoxifen is based almost entirely on the standard 20 milligram dose. And that dose was developed in cancer treatment trials. It was initially used in women with more advanced cancer and then as additional treatment after surgery in women with earlier cancer. In these cases, tamoxifen is very well-established for improving cancer outcomes. What we’re discussing here now is tamoxifen for prevention, and the calculus, the effect of toxicity in women who have had cancer and are offered a treatment for that compared to women who’ve never had cancer and are offered a drug for prevention of cancer in the future. That’s a different calculation. So, the toxicities that are very acceptable in women who are being treated are not so acceptable in women who have never had cancer. But I think it’s useful to divide those side effects of tamoxifen even among healthy women into two categories.

One is the quality-of-life side effects, and they are more common. So menopausal effects like hot flashes and sometimes sexual problems and vaginal dryness, those things happen more frequently. They’re ’tolerated variably by different women depending on their motivation. The serious side effects of tamoxifen are mainly twofold. One is that it results in a small increase in uterine cancer risk, and the other is that it may cause an increase in risk of blood clots. Those are seen mostly in older women. So for premenopausal women, those risks are really quite low and not that different from women who are not taking tamoxifen.

But for postmenopausal women, and particularly women in their sixties and older, those are serious considerations. Fortunately for that group of high-risk women, we do have alternative medications that don’t have these side effects. They have other side effects, of course. So as a general principle, the idea that we have to find the minimal effective dose rather than just doses that have been borrowed from treatment trials is a very valid principle, and that’s what many of us are working on. But yes, the tamoxifen risks are mainly quality of life, as I mentioned, and the uterine and clot risk.

Dr. Larry Norton: Judy?

Dr. Judy E. Garber: So I can’t believe it, but it’s time for the last question, which is about circulating tumor cells, circulating cell-free DNA. Last year, Funmi mentioned that among all this technology progress is the possibility that we could use a blood test to find cancer and, no offense Connie, skip the mammograms altogether. Where do we stand with that now? Does anybody want to comment on progress in blood detection?

Dr. Lehman: I hope it happens. I’m going to have you talk about how you think it’s going to happen, but as an imager, I hope it happens and it would be fantastic. We imagers have a lot of work to do in a lot of different domains, and if we have a simple blood test that can replace the mammogram, it would be fantastic.

Dr. Norton: Yes, I think it’s going to be an interactive, and I think there’s no “yes or no” answer on all of this. There are some already tools out there that look very, very promising because cancer is caused by abnormalities in DNA almost exclusively. Some of that DNA is spread into the blood, and by doing a blood test—and again, the technology has improved enormously about finding these abnormalities—it is possible you can find a piece of abnormal DNA and that might indicate that there is a tiny invisible cancer brewing somewhere. We’re still going to need imaging tests to find out where it is, I think. So I think there’s going to be an interaction in that nature. The other thing, which is not apparent—and we’re getting into a big topic when we have no time—is that as you get older, you’re going to get abnormalities in your DNA anyway, despite the fact that you don’t have cancer.

There’s something called clonal hematopoiesis, where you have actually mutations in your white blood cells that occurred as a function of age, and it actually does predispose you to developing things like leukemia. But most people have these abnormalities, and their blood cells don’t develop leukemia. And so when we actually measure DNA abnormalities in the blood, we’re identifying a lot of normal individuals who are never going to get cancer. And I think that even though they have those abnormalities, it’s just part of natural aging, so we’re going to have to be very careful that we don’t over-diagnose. And I think that all of our panelists have touched on some aspect of this, which again, the interactive-ness of the science, BCRF. If you have a known predisposition, if you have risk factors and you have a profile that suggests a higher risk and you have an abnormal piece of DNA, that’s going to have different meaning than somebody who doesn’t have that, for example.

If you have an abnormality that suggests, “Well, it’s most likely coming from the breast,” but very sophisticated imaging tools don’t show anything, then it may require further imaging tests or other tests in the future to follow that individual. But it also may indicate an opportunity for chemo prevention, cancer prevention with drugs. You have an abnormality, we can’t find it, but we have an approach to reduce your risk, and then we can follow that blood test and see if it disappears. And often with our cancer therapies, when patients have abnormal DNA in their blood, our cancer therapies make those abnormalities go down or disappear entirely. So it’s not any one thing. I’ll end with my favorite cliche. People ask, “What’s the most important part of what you’re doing?” And I say, “I’ll answer that question if you tell me what is the most important part of the airplane.”

Is it the left wing or is it the right wing? Is it the landing apparatus? Is it the navigation so that you land in Dubai and not in some other place where there’s a war going on? Which happened to me recently. The fact of the matter is it’s all important. What makes the airplane work is that all the parts work and they all work together. And that’s what BCRF is all about. We are developing all parts, everything that we can think of, everything that comes from the extraordinary intelligence of our investigators, everything that we learned from the field. We study the entire airplane, and we also want to make all the parts work together. And that’s why I am incredibly appreciative of this panel for bringing forward their ideas, for talking about their own work, for talking about the interactive-ness of it, and my colleagues in the room who are doing it as well. Please join me in thanking our session.     

That was BCRF’s 2023 NY Symposium and a special Investigating Breast Cancer podcast. Thanks for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.

Each October, BCRF holds its annual New York Symposium and Awards Luncheon. The event recognizes BCRF-supported investigators for their devotion to ending breast cancer and announces the Foundation’s research investment for the coming year.

This year’s program began with a symposium, “Targeting Cancer Where It’s Most Vulnerable,” featuring an expert panel of BCRF investigators who discussed novel breast cancer therapies, disparities, and what’s on the horizon in research.

The panel was co-moderated by BCRF Founding Scientific Director Dr. Larry Norton and BCRF Scientific Director Dr. Judy Garber. Joining Drs. Norton and Garber were panelists Drs. Lisa Newman, Andrew Tutt, and Maria Jasin, who received the 2022 Jill Rose Award for Scientific Excellence.

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Read the transcript below: 

Dr. Larry Norton: It’s been an exciting year of science and an incredible time for BCRF. The pandemic is not quite over yet as we all know, but we got through the worst of it and the organization stayed intact through the extraordinary team that is working.

This year, we brought in 12 new investigators under the leadership of Dr. Judy Garber, who I’m introducing here, BCRF’s scientific director. It’s really been an extraordinary time. I learned an astonishing fact, which is 90 percent of what we know about cancer we discovered in the last five years, if you are people who track these things in publications, it’s an incredible time of discovery. We have with us true world’s experts to discuss. We’re focusing on the topic of hitting cancer where it’s most vulnerable and all the large aspects of that topic. I’m going to ask each of them to introduce themselves and to talk about what they’re interested in, what they really think is exciting, and then we’ll have some discussion among ourselves, and as soon as possible, we’ll open it up to your questions. All right. The Rose Award winner who will receive special accolades is sitting to my immediate left, and I’d like her to introduce herself and say what she does.

Dr. Maria Jasin: Thank you, Larry. My name is Maria Jasin. I am a researcher at Memorial Sloan Kettering Cancer Center. I do relatively basic research and came into I would say the breast cancer field through the original identification of the genes and some relationships with a key protein that is involved in a DNA repair process that we had been studying. It’s termed homologous recombination. This DNA repair process is particularly notable because when there’s DNA damage, so for example, when the DNA is broken, then this process is a way to perfectly restore the sequence prior to the DNA damage. It’s a really critical repair pathway, and so it’s perhaps not surprising that disruptions of this lead to tumor predisposition. We’ve been working on these proteins, especially BRCA2, since our initial discoveries. There’s an amazing amount of things we know and also still an amazing number of things we don’t know, so we continue to study it.

Dr. Larry Norton: Okay. We’ll talk more about the importance of DNA and why DNA going awry is a problem as we move forward. Andrew?

Dr. Andrew Tutt: Good morning. It’s a real pleasure to be here. My name’s Andrew Tutt. I’m a clinician scientist, which means I am a practicing clinical oncologist, but I also had the opportunity to train in laboratory science during my development. My opportunity there was actually working with my mentor, Alan Ashworth, now a BCRF investigator. Long-term with Alan, now I’m joining the family as it were. We were trying to work on what the function of BRCA2 was after Alan cloned it. You’ve heard the amazing work of Maria to my right in that area, and then as a clinician trying to see how that might be usable in the clinical context, how that might change how we treated women who had breast cancer associated with the inheritance of those gene faults. A large group of people, labs, wet laboratory, scientists like Alan and Maria, geneticists, and clinicians running clinical trials came together over recent years in trying to develop a way of targeting the Achilles’ heel that these particular forms of breast cancer had.

I’ve been able to be part of that as that’s developed the concept of PARP inhibition using this synthetic lethality principle in order to develop a very individualized treatment approach using the weakness that these cancers have despite the fault in the gene leading to the cancer developing. This has been a really big year for that concept because the Olympia trial that I’ve had the pleasure of leading has been a huge cooperative effort. An organization led by another senior BCRF investigator, Dr. Martine Piccart, has worked with colleagues around the states, many BCRF investigators, Judy Garber to my left, Susan Domchek, many to ask the question, “Could a PARP inhibitor treatment improve outcome for women with early breast cancer caused by these gene faults?” The answer that’s come this year is yes, and this can reduce the rate of recurrence, life changing recurrence by over a third more women alive as a result of having access to this treatment, a new drug.

This is a big year. This is, I think, the result of collaboration that BCRF is so much part of bringing laboratory science and clinicians together, but we move on always to try and solve the new problem. It doesn’t always work. What myself and others working within BCRF are now trying to do is understand when this doesn’t work, why doesn’t it work, and develop the new treatments in that setting. One of those causes of why it doesn’t work is when the BRCA gene fixes itself. It caused the cancer, but then the cancer can learn how to fix that gene change. It’s called a reversion. When that happens, the cancer can escape PARP inhibitor, but in the process of fixing its Achilles’ heel, patching its Achilles’ heel, it potentially creates a new sign, a new flag that the immune system could recognize and be taught to act upon a new form of treatment approach. We’re trying to investigate could this be a new way of improving the outcome in this genetically defined form of breast cancer, and BCRF is enabling us to do that in a collaborative way.

Dr. Larry Norton: Thank you. Yes, I love your New Jersey accent by the way. It gives me a lot of confidence, I must say. Lisa? Lisa, you’re on.

Dr. Lisa Newman: Good morning, everybody. My name is Lisa Newman. I’m a surgical breast oncologist and chief of breast surgery for Weill Cornell Medicine, and I am also the founder and medical director for an international breast cancer team, the International Center for the Study of Breast Cancer Subtypes. My career focus has pretty much always been in studying breast cancer disparities, and in particular, studying the breast cancer impact on African ancestry communities. Today, it’s obviously wonderful that we can celebrate all the advances that we’ve made in breast cancer treatment and outcomes, but of course, we still are heartbroken over all the pain and suffering that this disease still causes. We are all also appalled by the alarming statistic that breast cancer mortality is 40 percent higher in African Americans compared to white American community.

Now, a lot of this breast cancer survival disparity is of course explained by socioeconomic disadvantages that are more prevalent in the Black American compared to white American community. It’s been a definite honor for me over the past 20 plus years in my career to work with wonderful community-based organizations such as The Sisters Network Incorporated, Tigerlily, Touch for the Black Breast Cancer Alliance. All of these organizations are doing wonderful, wonderful work in addressing breast health inequities, both at the patient awareness and patient education level and at the provider level because there are unfortunately persistent implicit biases and systemic racism that affects how we deliver breast cancer care. This results in the more advanced stage distribution that we see for breast cancer in African American women, and ultimately, this translates into some of these survival disadvantages that we see. There is also a huge gap that we have in research to understand the genetics specifically of African ancestry and how the genetics of African ancestry can also impact on breast cancer biology and breast cancer outcome.

This is why I’m so grateful to the Breast Cancer Research Foundation for agreeing to support some of the work of my team, the International Center for Breast Cancer Subtypes, where we’ve been partnering with researchers not only across different areas of the United States, but across different regions of Africa. We are specifically studying the genetics of African ancestry and its impact on breast tumor biology. About 10 years ago, we characterized the breast cancer burden of women from West Africa compared to East Africa and documented the fact that triple-negative breast cancer, which we see much more commonly in African American women, it’s also extremely prevalent in women of West Africa, in particular of Ghana where we see it accounting for about half of the breast cancers compared to East Africa where we see triple-negative breast cancer accounting for only about 15 percent of the cancers.

Now, all of us remember from our history classes, the transatlantic slave trade many centuries ago brought the ancestors of contemporary West Africans across the ocean, and so we, as African Americans today, have quite a bit of shared ancestry with contemporary West Africans, including Ghanaians, but we don’t have quite as much shared ancestry with East Africans including Ethiopians because the East African slave trade largely went further eastward to the Mideast and Africa. Our group is specifically honing in on the genetics of Western sub-Saharan African ancestry in understanding tumor biology of the breast. We did actually identify several years ago that a particular gene called the Duffy gene has a specific variant associated with Western sub-Saharan African ancestry called Duffy null, and we were able to document the fact that the presence of this Duffy null variant is specifically linked with the risk of having a triple-negative breast cancer compared to having a non-triple-negative breast cancer.

Our scientific director, the card-carrying and brilliant geneticist, Dr. Melissa Davis, who I recruited to be the scientific director for our international team, she’s been studying this Duffy gene for most of her career, and it’s been extremely exciting to learn that this Duffy null variant, which is linked to Western Sub-Saharan African ancestry, is associated with that ancestry because of its development due to evolutionary selection pressure in conferring some resistance to malaria. Malaria, of course, became endemic in that part of Western Africa because the tropical climate supports the mosquito life cycle, which is the perpetrator of malaria. The populations in that area were under tremendous evolutionary selection pressure to acquire any variance that would allow them to survive this deadly disease, but East Africa, actually, has a lot of higher altitude climates that don’t support the mosquito, and so the history of malaria is different in East Africa, and you don’t see this Duffy null variant to the same extent in populations with East African ancestry. Now, we are connecting the dots between this Duffy null variant, West African ancestry, and triple-negative breast cancer, and the effect of this Duffy null variant on the inflammatory landscape of the mammary tissue microenvironment. Very, very exciting work and we are really optimistic that it’s not only going to teach us more about the biology of breast cancer disparities here in the United States, but it’s also going to develop novel insights regarding the pathogenesis of this biologically aggressive tumor, triple-negative breast cancer. Coming all the way back around to social determinants of health and health inequities, we also see that there is a lack of diversity in our medical, our cancer research workforce.

By improving the diversity of that workforce, we’re also optimistic that we will have better and more robust disparities research. That’s why I’m also very proud and happy and grateful that BCRF has agreed to support a very novel breast cancer consortium where my international team will be partnering specifically with the black members of the American Society of Breast Surgeons to develop a more robust biorepository to better understand the genetics of triple-negative breast cancer and African ancestry. Thank you for your time and attention, and thank you to BCRF.

Dr. Larry Norton: Judy, you’re co-moderating, but also, you’re working in this area as well. Do you want to just tell them a little bit about what your work is before we have some more internal discussion?

Dr. Judy Garber: I’m Judy Garber. I’m also a breast oncologist and a clinical cancer geneticist at Dana-Farber. I have worked with Andrew on the Olympia trial. We also are interested in how we can help make cancer genetics more accessible for many communities and how it can help the medical community in general to help their patients understand when they might want to be tested, how they might use the information. Then our work has focused a lot on the prevention side, trying to understand not only the surgical approaches to risk reduction, which we all understand are effective, but not necessarily what everyone most wants to do, and looking for alternative medical therapies that we might use.

I would say that within BCRF that our job in part, Larry’s and mine, and our scientific advisory board is to find the most talented, most effective, most passionate researchers across the spectrum of work that will bring progress across all the areas in breast cancer where we need that progress. The addition of new investigators is a huge step forward in that regard. We’ve always been able to do it before. A few years into the pandemic, it’s been harder, but we’re thrilled to be able to be back on that track again.

Dr. Larry Norton: Wow. We’ve covered a whole lot of things here, and if you hear specific things like what is triple-negative breast cancer, write down the question so we’ll get back to that, but I think many of us in the audience know that these are breast cancers that don’t have the estrin receptor or progesterone receptor or HER2, and they tend to grow more rapidly and we don’t have specific targeted therapy yet for them although, I guess, Olaparib would have to be considered a targeted therapy. It means that’s a PARP inhibitor going forward. I’m going to ask to define exactly what we mean by PARP inhibitors in a second, but I just can’t help but do this, is that I was very unconvinced when I was a younger doctor that there was such a thing as familial breast cancer, and I thought that probably the environment was the dominant feature.

Obviously, we’re learning the genes that you inherit and the environment you interact called gene environment interactions and lead to all sorts of diseases, and not just breast cancer but other cancers and heart disease and many other things, and understanding what we’re carrying in our genes and its relationship to the environment is important. We heard this fascinating story where a certain mutation that can give you an advantage in a place where there’s a lot of malaria can actually cause problems when you’re in a place that doesn’t have malaria. Those things are important, but I was unconvinced. I thought the environment was really more important just as the thing is, and I had to be convinced that there was such a thing as abnormal genes that you can carry that could predispose to breast cancer. The breakthrough occurred because of Mary-Claire King, who’s sitting right here, who really nailed it that there was a place in our genome, in our genes that was abnormal that people could carry and that could lead to cancers.

That started not only everything that we’re doing in terms of susceptibility to breast cancer and to other cancers, but this whole relationship between the genes that you can inherit and your sensitivity to drugs and the instant disease. It was really a major turning point in my life professionally and I think all of our lives because it’s just uncovered so much of what we now discover, so thank you, Mary. I just want to get back to this thing about PARP because we threw the term out without a specific meaning. Maybe, Andrew, explain exactly what PARP is and why it’s important in this context.

Dr. Andrew Tutt: PARP is what we call an enzyme. It’s a protein and it’s a really important part of how cells do many things, but one of the things that it does is it creates a polymer network of proteins around our genetic code DNA when it’s damaged. That gets used as a scaffold to bringing other business building blocks needed to repair our genetic code if it gets damaged. The drugs, the PARP inhibitors, stop that scaffold being formed, but also gum it up and stick it on the DNA in a way that our cells normally handle if they’ve got their BRCA genes working, but the tumor cells in someone with a gene fault in BRCA1 or 2 don’t have that working. That’s how the cancer developed, but it means that’s the Achilles’ heel. If you stop that scaffold forming properly, you gum it up on the DNA and you don’t have your PARP working the cell dice. That’s the cancer cell that’s dying. The normal cells of the person, quite happy. That’s how the concept of synthetic lethality works. Gum up the pop, stop it working, and selectively kill the tumor cell.

Dr. Larry Norton: Maria?

Dr. Maria Jasin: Well, it’s interesting. We focus on DNA repair and the specific roles of BRCA1 and 2 in this process of homologous recombination that’s very precise, but then there are ways of getting around this deficiency to some extent to allow tumor cells to survive, but even the idea of hitting a second DNA repair pathway so elegantly with PARP inhibitors turned out to be more complicated. It’s really this instead of necessarily losing another DNA repair pathway, it’s gumming things up, as Andy said.

We learn more and more about these things as we go along, and then PARP inhibition having perhaps other effects like affecting the immune response and things. We need to keep going forward and not just be satisfied with the simple original papers that are out there, but really to delve into things more deeply to understand why there are issues with treatment being unsuccessful or how reversions develop-

Dr. Larry Norton: Talk about reversions for a second because I think that’s a more difficult concept. What does that mean?

Dr. Maria Jasin: Okay, a simple way of thinking about it is you have, for example, a BRCA2 mutation that disrupts this process of homologous recombination, but then that can be a mutation that truncates the protein so you only have half of the protein, but then a mutation can occur in the DNA that allows the rest of the protein to be made, and so then as if you have a functional protein again. That’s one way of getting reversion, and that’s a real problem that is often seen in BRCA1 and 2 tumors that are treated with PARP inhibitors or platinum drugs, but then there are other ways that are often not understood of how initially susceptible tumor to a PARP inhibitor then becomes refractory to treatment. That can be through completely different pathways, and some of these we know, and then some of them we don’t, and so that’s also a very active investigation because, obviously, it’s so sad when a woman is successfully treated with a PARP inhibitor and then becomes resistant to it, so it’s a major clinical problem.

Dr. Judy Garber: I think Lisa wanted to say something.

Dr. Lisa Newman: This is such an incredibly important conversation regarding PARP inhibitors and BRCA status and BRCA testing, and so I have to just make a plea in favor of our addressing the fact that African American women historically have been under genetic tested, and so we don’t have as robust an understanding of the BRCA patterns in the African American community as we need to have. Historically, we’ve seen that African American women are more likely to have these patterns that we call variants of uncertain significance in the BRCA genes, which are genetic patterns that we just don’t understand how they fit into cancer risk, and in particular, triple-negative breast cancer risk.

Women with these VUS, which includes a lot of African American women, will not derive the benefits of PARP inhibitors because we don’t understand if they are just as beneficial or not and women with variants of uncertain significance. I’m glad is here. She’s also been funded by BCRF and Funmi [Olopade] has done some wonderful work to try to better understand BRCA status in black women, so just a plea for all of us to work harder at more genetic testing in diverse communities.

Dr. Judy Garber: Thank you. Andrew, maybe you could tell us a little bit. You’ve heard that PARP inhibitors have become an essential element of treatment that we didn’t have before, and I think in a reasonably short time, and now we know that they don’t work completely all the time. Where are the most important places, we’re going now with PARP inhibitors? Can they replace chemotherapy sometimes? Their pills? They’re easier to take? What do we do when resistance emerges as often happens in our targeted therapies?

Dr. Andrew Tutt: Thank you, Judy. I think we have several opportunities. I think one is, as exactly as you say, to not congratulate ourselves collectively too much for what we’ve achieved, but also say, “Right, how do we make it better?” Because so many women now will be receiving these drugs in the early breast cancer setting as well as sadly in advanced disease, we can work with them to try and understand the differences between those that they work well and longer for and those who they’re not working for, and study that in the laboratory to bring together what we call forward translation, understanding from the Petri dish what can cause resistance to PARP inhibitors, and reverse translation which is coming back from the clinic and saying, “When we take blood and we look at tumor DNA in the blood or we analyze biopsies deeply, what is really happening in the clinic with women having PARP inhibitors?” Bring those two things together and study what are the most important things we need the science to focus on solving when it doesn’t work?

What that is beginning to tell us is that one of the causes of these fix-up mutations, these reversions may be the use of another form of DNA repair. Dr. [Alan] D’Andrea, one of the BCRF investigators, others in our research center, Alan Ashworth’s group that’s still interested in this area, is using a different repair process that actually causes the cancer to create these fix-up mutations, but if you drug that, you might have a different Achilles’ heel, kill the cancer in a different way, and stop the resistance happening. Studying this reveals the new Achilles’ heels. I think the other opportunity is in the other direction. It’s saying when this works really well for women, maybe we can back off. Maybe we can back off that chemotherapy. Maybe we can avoid the chemotherapy at all or replace some component of it that is particularly challenging or causes most side effects with the PARP inhibitor instead. We must look for both of those needs and opportunities, and that’s what’s happening.

I think the thing that’s so exciting, and the thing I think BCRF enables better than any is the bringing together, it’s what gets me out of bed in the morning, is bringing together the power of fundamental science and fundamental scientists with clinicians and trialists and our patients, women with breast cancer, to crack this. It doesn’t always have to be in a clinical trial. It can sometimes just be in practice. When people are being looked after, they sign up to the idea that you would study their blood, you’d study any biopsies after the pathologist has finished the diagnosis to really try and understand this. This is now going to apply to thousands of women around the world of all sorts of different ethnicities, geographical locations, and it must involve all of that diversity, otherwise we’ll be studying something very particular. That is our opportunity. That is what I think BCRF enables to happen through these scientific meetings, and I think it’s amazing as an opportunity.

Dr. Larry Norton: That actually was the core idea that underlined the founding of BCRF. We were seeing an explosion of laboratory science that looked like it could be relevant, superb doctors and clinical investigators who had the capability of testing things, but the two communities weren’t really communicating very well, and to bring those communities together is what really what BCRF was about from the beginning, and really, it’s worked, obviously. The extraordinary collection of investigators you see that is spread around the room, the periphery of the room, really attests to that and the advances that have actually occurred. This is a question that I’m asked a lot in this regard. You’re studying BRCA1, BRCA2, you’re studying this PARP, and things like that, but I don’t carry an abnormal BRCA1, I don’t carry an abnormal BRCA2, or other genes that I think we’ll get to that may predispose. How does this research relate to me and the kind of situation that I’m in? How do we answer that question?

This is studying special populations, all right? By the way, European Americans are a special population. It just happens to be a majority population, but it’s a special population. It’s a minority of the world that can trace their ancestry to Europe. It just so happens that we have a concentration of them right here in the United States, and so in that kind of thing too, but if you look at the world population, it’s actually a minority. All this work that we’ve done on people of European descent, how does that relate to people who, their ancestry goes back thousand years in Asia and so on and that forth? How are we going to take this knowledge that we’re gaining out of special populations and extend it to the entire world? Judy, look like you’re going to respond to that.

Dr. Judy Garber: I’ll give a small beginning. Maybe Lisa will add. I think at the most basic levels, you could say that it’s very difficult always to know where the next breakthroughs will come from, and that the more we understand the fundamental workings of the genes that predisposed to breast cancer, the genes that determine   breast cancers, the genes that are involved in fighting breast cancer, the immunology of all of this, that the more we understand in some groups, the smarter we hope we’ll be about understanding other groups. Then still there are surprises. I would say this year, a big surprise was that one of the drugs developed for the treatment of HER2 positive breast cancer.

There are many people here today, Ian Krop and others, who’ve led the way on these drugs, but one of these drugs targeting HER2 was shown to be extremely effective in triple-negative breast cancer, and to suggest that maybe some of the tumors that were HER2, which required they be high HER2, that ones that were low HER2 might also benefit, and even the triple-negatives where there’s no HER2. That’s a surprise. That’s an opportunity you have to sort out. For the study of genetics, there have been genes that we didn’t expect to be involved in breast cancer. NF1, that’s not a gene we link to breast cancer, but it is, and now we have to understand why and then can expand from that what are the populations where this might be more important? That’s not a defensive discussion of genetics, but it is true overall. That is as smart as we think we are, we always have more to learn, and that’s really why the most basic science is still important to contribute to breast cancer. We just don’t always know where the next breakthrough will come from.

Dr. Larry Norton: Yes, that’s my favorite Mark Twain quote. It’s not what you don’t know that gets you into trouble. It’s what you know for sure that turns out to be wrong. It’s always an evolving pattern of knowledge. I got to say my own view on this is, and just to interject since we’re having an informal conversation among our friends here, is that what I’m very impressed with is that the genes that survive evolution are the genes that affect more than one process because the multiplicity of things is really what’s gets rewarded by the evolutionary process. The more and more we learn about genetics, we learn that we think we understand this gene does this thing and then does this consequence and this approach, but it does many other things. The relationship between the immune system, the relationship to the other cells that are in the cancer, these are all things that we’re discovering.

My own view is that the simple way that humans think, A goes to B goes to C, is probably not going to get us really the same kind of comprehensive answer to these puzzles that we suspect that we’re going to have to use more sophisticated ways of using data, so I’m doing a lot of stuff with mathematics now to try to actually look at complex systems and predict complex systems that are not necessarily intuitive, that things that are not intuitive or often true, and things that are intuitive or sometimes wrong. We have to look at more novel ways of looking at complex processes and it all relates together to our understanding of genes, understanding of fundamental biology, understanding of how they could be perturbed and what happens actually in the clinic, and how this relates to the genes that you may inherit, and how that relates to the environment and the social situation you’re in.

Chronic stress, chronic unemployment, food insecurity, all those things are going to affect your biology and are going to have those things, so understanding this complexity is something that I’m really very much immersed in now and trying to derive tools that we’ve used for studying it, but also be able to predict in the individual what could help them and why they’re not getting helped. I’m starting to think that eradicating the last cancer cell in somebody who has metastatic disease may not be the right goal. Well, the right goal may be to get down to a very small number of cancer cells and ever prevent them growing to a large enough number that causes trouble and achieving what I call low level plateau of cells. That may be more achievable thing that Silvia Formenti and I were talking about immunological approaches this morning to use the immune system to try to accomplish this as well. All of this is really related, and all fundamentally connected.

Dr. Lisa Newman: Our research team coined the term “oncopologic anthropology” to try to understand this interplay between population migration and genetics of ancestry and subsequent cancer risk. Earlier, I commented on the connection between the Duffy null variant and malaria being endemic in West Africa and so resulting in this variant that confers some resistance to malaria that’s seen in any individual that has Western sub-Saharan African ancestry, but I do also want to comment that this type of evolutionary selection pressure is something that has occurred across the globe, and populations, our ancestors everywhere had develop different variants allowing them to survive different climates, different altitudes, different food sources.

The general public has actually been way ahead of the cancer research community in showing their hunger, their appetite for understanding these ancestral genetics because when people purchase those commercially available kits to spit into a little container and send it off and get a report back regarding where their ancestors came from, those reports are very oftentimes reflecting some of these genetic variants that were acquired by our ancestors as a function of evolutionary selection pressure in different parts of the world, but we see those variants today expressed in current generations regardless of where they live. We have to start harnessing that technology to understand how these variants can also impact on the inflammatory landscape of different organs and subsequent cancer risk.

Dr. Andrew Tutt: To come back to your question about the relevance of some of the perhaps very discreet group of women who have inherited gene faults in the BRCA genes that cause this defect in homologous combination.

Dr. Larry Norton: Homologous combination? What is that?

Dr. Andrew Tutt: I’m nervous even trying to describe this with the amazing scientist to my right, Maria Jasin, next to me, but it is as Maria described, a very accurate way in which a cell can repair its genetic code when it’s damaged. Damage happens to our genetic code all the time. We are housekeeping our genetic code all the time. Breaks in the DNA code are dangerous to the cell so it’s developed ways of housekeeping it really well. Some are kind of, “Let’s do a quick clean up and just put it back together. Someone’s coming around to the house and have a look.” It’s not very good cleaning. Others are really pernickety accurate ways of cleaning up DNA. Homologous recombination is the most accurate way of getting the house back in order. When it doesn’t work, you’ve got a messy house and your genes don’t work properly and bad stuff starts to happen. You need it working.

Dr. Larry Norton: Maria?

Dr. Maria Jasin: I think one thing that is hard to appreciate perhaps is that we learn about DNA in school. It is the basis of life providing all the codes we need to develop during pregnancy, growing up, et cetera, to form all these tissue types in the body yet, so we focus perhaps in school a lot on how important DNA is in this mode of transmission, but forgetting that actually every cell DNA and every cell in our body is constantly being damaged from a number of different processes. There’s this race to there’s damage and then the cell is repairing the damage as a matter of course, and so there are some times when we’re clearly exposed with radiation to agents that are going to damage the DNA, but just the normal cellular processes lead to a lot of DNA damage, and that’s why these processes are just so important to work normally.

Dr. Andrew Tutt: The recombination group is bigger than just the defective cancers that have a defect in that process. It seems to be a much bigger group than just those who’ve inherited mutations in the gene. We can now understand that that could be as much as a third of people with triple-negative breast cancer even if they haven’t inherited a mutation. Try to study how the BRCA1 gene, for instance, is turned off rather than damaged, mutated, makes that relevant to a much higher proportion of women with breast cancer and potentially a significant proportion of those with triple-negative breast cancer even if they don’t have the familial form of it.

Dr. Larry Norton: One of the things that BCRF supports is a cooperative group of hospitals that work together on cancer problems, particularly the focus on breast cancer, called the Translational Breast Cancer Research Consortium (TBCRC), and it’s led by Antonio Wolff. That group did a clinical trial that made an interesting discovery that, I think, is very relevant to this question. Stand up, Antonio, because I see you.

Dr. Antonio Wolff: Thank you, Larry. The Translational Breast Cancer Research Consortium, which receives a significant amount of funding from BCRF, had a study called TBCRC 048, and Dr. Judy Garber and Nadine Tung led the study, and it showed that in many patients who did not have a germline mutation in BRCA1 or BRCA2 but went on to develop a tumor that developed a specific mutation in those genes could then potentially receive treatment with a PARP inhibitor. This was a major discovery showing that you don’t have to be born with a germline mutation to potentially benefit from these tumors. These mutations can quite commonly happen, and if they do, all of a sudden it becomes a new targeted treatment. We are beginning to understand that breast cancers not just traditional phenotypes, ER-positive, HER2 positive, and triple-negative, but understanding the molecular profile of individual cancers can really tell us a lot about new treatments that could potentially be used, some of which derive from the wonderful work that we are hearing today about.

Dr. Larry Norton: Right. Thank you. Thank you very much. Actually, that gives me a segue into something else. So much of what we’re learning about the genes and the relationship between the DNA in the cells and the cellular function is dependent on a technique that’s been developed for actually changing genes and looking at what those changes do. How does the gene function? Well, you can change that gene and see how it functions differently, and then you can understand those gene function. This got a lot of something called CRISPR-Cas9. It’s a technique for actually editing genes in the laboratory. There’s actually some clinical applications of it now really as well. None of that would’ve developed without the work of Maria Jasin. Maria, talk to us about that discovery of yours.

Dr. Maria Jasin: Well, this is CRISPR-Cas. You’ve probably heard of The New York Times talk about it a lot. This sounds counterintuitive from what I said earlier, but it’s a way of introducing DNA damage at specific sites in the genome. We didn’t develop CRISPR-Cas ourselves, but years ago, in this ’94 paper showed that if we put DNA damage to a double-strand break in the genome-

Dr. Larry Norton: That DNA is two strands, one from mom, one from dad, basically sort of simply. This is a clean break across both those strands of DNA, double-strand break.

Dr. Maria Jasin: This double-strand break, so the DNA is broken that the cellular repair processes then can repair it and it can repair it imprecisely or precisely by homologous recombination. Having then many years later this tool being developed, CRISPR-Cas, that can put DNA damage anywhere in the genome to change the genome the way you want, has really been a powerful technique to address all sorts of questions and is being used in therapeutic processes, CAR T cells, for example, for immunotherapies. This is why the Nobel Prize went to CRISPR two years ago. It really changed how people could do experiments. It really accelerated the ability to do a whole slew of experiments, as well as not just experiments, but actually going to the clinic and treat patients with it.

Dr. Larry Norton: Maria should have shared that Nobel Prize, but instead, she won the Shaw Prize, which is the equivalent of the Nobel Prize given out in Hong Kong, so thank you for that discovery.

Dr. Judy Garber: The Nobel Prize did go to two women, so we’ll take that. I think one of the other things just to remember for all of us is that the BRCA1 and 2 genes, and the PALB2 genes, and these other genes we’re learning about are not only for triple-negative breast cancer but also for some hormone receptor-positive breast cancers. I just wouldn’t want our conversation to feel like it’s really only about the benefits to triple-negative disease. That’s not the case. One of the things that we have to learn about is which of the hormone receptor-positive breast cancers might these drugs work for? The ones related to these genes that are from inherited mutations as we’ve heard, but what else? It is more broad than just triple-negative.

Dr. Larry Norton: Right. Thank you. We’re going to go to Q&A now. Do you want to do the first question, Judy?

Dr. Judy Garber: I will. The first question for Dr. Newman is certainly there’s more work to be done in African American communities related to breast cancer. What can African American triple-negative survivors do to help? I would broaden that to ask what can breast cancer supporters and survivors do to help science?

Dr. Lisa Newman: Thank you for that wonderful and very important question that we definitely need to address because our patients, our survivors do have an incredible energy and desire to contribute to all of the work that’s being done and to helping design better work because our survivors understand firsthand what the needs are, where the gaps are, so we definitely need to listen to our survivors in the design of research. To breast cancer patients in general, and especially patients from diverse communities, it is incredibly important for us to make sure that we spend the time educating the public regarding the power of research and clinical trials. Being in a clinical trial for a breast cancer patient doesn’t necessarily mean being in a study where your treatment is going to be randomized. It can be as basic but yet equally powerful as contributing tumor tissue or your clinical medical information to a biorepository, a biobank, a registry study. All of this information is important and necessary.

Dr. Judy Garber: Thank you. Larry, do you want to talk about AURORA?

Dr. Larry Norton: Well, yes. Martine Piccart is here somewhere in the room, our longstanding colleague from Brussels and a great doctor, but a great organizer of clinical research. She and I were standing in the back of the room at a BCRF-funded meeting, and I think it was in Brussels. We were hearing presentations about the molecular biology of breast cancer. We’re talking about DNA mostly, and RNA, and what are the really important molecules that make cancer cancerous. Everything we’re talking about genes. It was just the dawn of the basic understanding of that. We were both impressed with the fact that all the studies were in DNA taken from tumors from the breast, that a tremendous amount of information was starting to be gathered about the nature of the cancer in the breast. It occurred to us in conversation that that probably was not the right question because it’s trying to figure out why the cows are in the field by only studying the cows that are still in the barn.

It’s the cancer cells that spread to other parts of the body that’s where the lethal cancer cell is. If it stays in the breast, it would be a lump, but it would never bother you. It would be a large pimple and would never really bother you. What do we know about the DNA abnormalities and other molecules, RNA proteins in cancers that have spread to other parts of the body? It was a very important question, but it would require an enormous amount of organization and international cooperation to achieve that, which means it would require will and intelligence but also funding. A great tragedy in all of our lives was the passing away of Evelyn Lauder, co-founder of this activity that we’re in right now. Her husband did a remarkable thing to start this off in discussion, which is basically he took her high-end jewelry and auctioned it and gave all the money into a project called the Founder’s Fund for exactly that study.

That generated the AURORA studies because the complexity of exchanging data and information across the Atlantic. We have an AURORA in the EU and AURORA in the U.S. for actually studying the molecular biology of metastatic breast cancer. It took an enormous amount of organization, and many of you around the room, many of the colleagues have been involved in this activity, the TBCRC that Antonio just mentioned, and Nancy Davidson in terms of her enormous organ organizational ability, and Chuck Perou in terms of his enormous skill in analyzing DNA and DNA modifications. We launched this international activity that has just been absolutely remarkable in terms of what is actually discovered. Major publication on the European side, a major publication on the US side just happening now, and learning about the genes that go awry in metastatic disease.

An important finding on both sides of the Atlantic is the importance of the immune system in the progress of cancer that spreads from the breast to other parts of the body. It relates to everything else that you’ve heard about here. It’s all connected and that’s really what BCRF is really all about is connecting the dots. We have still more work to do to complete our project and that’s really underway, and the funding of that is committed and further funding being arranged. That’s really where that particular project is going. It really shows you the power of organizations like this and the power of your support of these kinds of activities to really make a difference and really make progress.

Dr. Judy Garber: And the willingness of patients to participate by giving their samples.

Dr. Larry Norton: Right. Yes. Again, that’s another one of this is that everybody on earth is either an actual or a potential cancer patient. We’re all together and everybody on earth is either an actual or potential healer, and that we can control so that we all have to go onto the healer side of the equation in terms of our activities. That’s what you’re all doing today. Everybody in this room is a healer and contributing everything they can in terms of their skills, in terms of their support, and working together toward the process. We’re just a large community, and the arc of that activity is moving rapidly towards progress. We have a lot more work to do. We have to work on the equity situation, and we have to work on advancing science. We have to make accessibility greater, but we’re moving in the right direction. If I sound a little emotional, it’s because I am on this particular topic. We’re moving in the right direction, and I just basically thank you all for working together towards this really commendable goal. Thank you.

Okay. Amy wrote a question as we’re talking about triple-negative breast cancer, which we defined as not having estrin receptor, progesterone receptor, or HER2. Are there other different types of breast cancer? What’s happening in the space of breast cancer subcategorization and how does it relate to our understanding of genetics? It’s a huge topic and many of us are really working on this topic as well. Actually, Chuck, are you here? Yes, let me get your answer to that.

Dr. Charles Perou: Certainly, within triple-negative breast cancers, we can subset them a number of different ways. One is using gene expression profiling, which I’ve been doing for many years and certainly many others in the audience. There, we can see there’s at least a couple kinds. One, we call basal-like breast cancer, which actually has significant similarities to serous ovarian cancer and lung squamous cancer, so we can see common themes between what you might think are different cancer types, but actually, they have many similar gene expression features, and they have many DNA somatic mutation features as well. We can also subset the patients according to the types of DNA mutations they have. Particularly, those that are therapeutically actionable are the most important classification tools. There, we had wonderful discussions about a subset of triple-negatives being BRCA1 or 2, faulty or not. I think yet other means that Larry alluded to is the immune system.

We’re going to now classify patients and tumors according to the activity of their immune system. If they have certain immune characteristics today, they’re going to get a certain class of drugs. If they have other characteristics, they seem poised to potentially interact with the immune system and we’re going to give them additional activators. I think you can see we’re now beginning to classify all tumors, not just triple-negatives, but all breast cancers according to the phenotype of the tumor, according to the DNA of the tumor, and according to the immune system, and in some cases, according to the genetics of yourself. We’re just getting better and better at this personalized medicine. Actually, you can see there’s going to be interactions between these as well. It’s very exciting times and I think we’re just going to get finer and finer clinical bins and better outcomes.

Dr. Larry Norton: Chuck, thank you. The first time we did this, breast cancer was really very simple. I remember the time, as Marc Lippman, who’s also in the audience, and I were talking earlier before we knew about the importance of the estrin receptor, but by the time BCRF was formed, we always knew that there was some tumors sensitive to hormone therapy that had estrin receptor and some not. The classifications were really very simple. We’ve just had this explosion of our ability to subclassify cancers and to understand their DNA abnormalities, understand links to hereditary susceptibility, and so on.

This has created a huge mountain of data with answers in it. The answer is somewhere in that data, but how are you going to get the answers out of that data? We’ve had a lot of discussions in BCRF about how we can approach the accumulation of the information from AURORA, the accumulation of further information that you’ve heard about, and really not only be able to analyze it ourselves, but release it to the world in a way that properly vetted scientists can look at the data. I’d like to ask Dorraya El-Ashry, who’s our chief scientific officer, who’s right here, to stand up and just explain in a very few minutes what the data hub that we’re organizing is all about.

Dr. Dorraya El-Ashry: Thank you, Larry. Yes, we’re at a very exciting time. You’ve heard about all of this tremendous data that has been accumulated over the last decades and the progress that is just at a tremendous pace right now. You heard from Chuck and from Mary-Claire about just tremendous amounts of data, big data that has been accumulated from all of these studies and on the stage from these clinical trials. We, at BCRF, where a part of our foundation is also collaboration, have just launched the BCRF Global Data Hub. What this will be, will be a cloud-based, computer-based system that will have in it at as its first phase all of the BCRF-funded breast cancer data sets, whether that’s laboratory-based data, whether that’s clinical data.

Whether that’s DNA analysis data, all of the BCRF-funded data sets that will then be available for BCRF-funded investigators to go into this portal and analyze the data, analyze their data with these other investigators’ data, and in this way, take this mountain of data that while each investigator is using for their own research, but vastly underutilized in terms of, as Larry mentioned, the answers being somewhere in there, and move it forward to greater impact. In the second phase, we will open it up to data from the breast cancer research community of other investigators so that this will be then the largest data hub and collection of breast cancer data sets available for breast cancer researchers to analyze.

Dr. Larry Norton: Thank you.

Dr. Judy Garber: Here’s a question that we haven’t touched on before which is where are we with liquid biopsies to detect metastasis or to detect breast cancer? Can you explain what’s a liquid biopsy and then how can they be used?

Dr. Andrew Tutt: An excellent question. I think there’s a huge excitement in the field around this concept of liquid biopsies, so what is that? This is taking a relatively simple blood sample, and in general, spinning it and having what we call plasma, the clear fraction of that, and looking in that for DNA that has come from tumor, and then analyzing to see, one, is their tumor DNA? Because that might tell you something about whether someone has still got some cancer on board as it were. Also, more deeply, what does it say? What is the fingerprint of the cancer that you could read from that DNA in the blood? Liquid biopsy could give you both of those things. Where is the status of that at the moment? I think in my own view, and it’s not my special area of research, we’re probably more advanced in using the information in people with advanced breast cancer as a way of perhaps sometimes avoiding an actual needle biopsy, and yet having very useful information about the tumor that could guide treatment.

There are approved liquid biopsy tests that could give the fingerprint of the cancer and inform the oncologist as to an option for targeted drug treatment. That might be a PARP inhibitor if a BRCA mutation was found in the tumor. It might be a PI 3-kinase inhibitor in ER-positive breast cancer. It might reveal something about the HER2 gene. This is useful. I think this is probably ready for primetime. The other part of the question is for detecting the recurrence of cancer. There is the potential that this liquid biopsy could be so sensitive that it could work out when someone has maybe finished their surgery and maybe their chemotherapy treatments. Do they need more? Do they need more treatments? Would it be better to catch that presence of cancer in the system early rather than wait for inevitable recurrence?

There’s a lot of work in this at the moment, and the assays are getting better and better, and it looks promising that one may be able to pick up recurrence earlier than someone becoming ill and it becoming detected on a scan, but it’s not yet completely clear whether that is sufficiently accurate to give someone that diagnosis of metastasis early and whether you are going to change their outcome by knowing it early and doing something about it. It’s still a matter for research. I think many people believe hugely important research much going on. I think if people can ask about this when they see their oncologist could they be involved in research, what is the relevance to them, I think it’s really good.

The final comment I’d just like to make is Dr. Norton was describing the AURORA program and the importance of understanding biopsy. Liquid biopsy is great. It tells you a lot. At the moment, it mainly tells you about DNA. DNA is really important, but how cancer behaves, a lot of that is to do with more complicated things to do with RNA, the messages in cancer, and the proteins that actually do the business, and in fact, what cells are talking to each other, and how the immune system is perhaps orchestrating immune response. You don’t get that at the moment through DNA in the blood. We think you can get much more of that now from biopsies in the complex study of biopsy. Real biopsy is still important. The two complement each other.

Dr. Judy Garber: Thank you.

Dr. Andrew Tutt: Thank you.

Dr. Judy Garber: I would just add that Andrew raised the question, can you use this as an early detection tool? Can we find cancer so early in patients that it’s not yet a lump detectable by imaging or in any other organ? Can you look for all cancers at the same time? That would be so efficient. We could stop those annoying colonoscopies. I don’t think we can stop the colonoscopies because not only are they early detection, but they’re also prevention. If you take out those polyps, then you don’t get colon cancer, so it’d be nice to have a few more of those.

I would say this has been a very exciting time. There are a lot of mostly companies trying to develop these tests and they have great potential. I certainly hope that in my lifetime, that I’ll be able to avoid some uncomfortable imaging in favor of a blood test, but we have ways to go. Like many things, you can see that the future of this is likely to be wonderful, but for the moment, especially for breast cancer, 30 percent sensitivity’s not good enough. We do much better with those uncomfortable mammograms and annoying MRIs than we can do with blood tests, but stay tuned because I’m sure that just as there will be progress in using these tests in treatment, there will be progress in using them for detection.

Dr. Larry Norton: Well, we always get practical questions also in terms of sophisticated theoretical ones, as you’ve heard. Lisa, you’re a breast surgeon. What do you think about breast self-examinations? People in the audience are getting confusing messages of breast self-examination. What is your feeling about that?

Dr. Lisa Newman: Yes, what a great question. The American Cancer Society really did move away from the recommendation that we used to all be very, very passionate about educating women about the monthly breast self-examination. They moved away from it many years ago because it did become apparent that the breast self-examination is tricky. All women will have some degree of lumpy bumpiness in the breast because that’s just the way the breast tissue is made up, fatty tissue, glandular tissue, ductal tissue. With all of the hormonal cycles from our ovaries, those tissues cause differences in ridges of the breast. Once a woman thinks that there might be a change in her breast exam with that monthly evaluation and she sees her physician, it’s really hard to unring that bell. If a possible abnormality has arisen, it can unfortunately lead to a biopsy that might have been unnecessary if the woman was actually detecting a normal variant in her own breast.

The exam is tricky and that’s the history behind why the American Cancer Society moved away from monthly breast self-examination. It does tend to result in more biopsies. However, I don’t think that we can abandon it completely. Women are going to be more in tune to significant changes in their breast compared to any clinician that’s seeing them once, twice a year. We do need for women to be aware of changes in their breast. I continue to talk to women about the “danger signs of breast cancer,” new lump in the breast, lump in the underarm, bloody nipple discharge, changes in the skin appearance of the breast. When those changes develop, you do need to seek medical attention promptly to get it worked up. Don’t panic because those symptoms can also be caused by benign problems, but we do need for women to be aware of changes and to seek medical attention promptly when a change develops.

Dr. Larry Norton: Good comprehensive answer. We’re getting down to the time limit. Last question from Judy.

Dr. Judy Garber: We’re actually going to have to ask Bob Vonderheide to stand up because the visionary question is what’s happening with breast cancer vaccines?

Dr. Robert Vonderheide: Thanks, Judy, and thanks for the question. The big picture is that immunotherapy is now available for some women who have different types of breast cancer, and it’s opened our eyes to having more opportunities as we do across all cancers to use the immune system. You asked specifically about a cancer vaccine. We think that one of the problems, one of the challenges has been that the immune system for most women with breast cancer is not reliable to fight breast cancer and we need to actually activate an immune response, and so there’s a lot of work. We had a discussion yesterday at the symposium about all sorts of great new ideas, that are in clinical trials. They’re not available. They’re not prescribable. The great visionary possibility as we learn more is can we use a vaccine for women who are at risk for breast cancer? Healthy individuals?

When we take this concept to our infectious disease colleagues, they don’t think it’s visionary at all because this is how we use vaccines, to prevent, and it’s what you alluded to before, Judy. Can we use something other than surgery to prevent breast cancer in the first place, or if a woman is at risk for breast cancer and has very early lesions but is not yet invasive breast cancer, can we intercept those lesions and reset the clock and send things back? This has attracted a lot of attention. There were articles recently in The New York Times and Time Magazine, which we can refer people to. I think it’s like the car, the mirror. Things are a lot closer than they appear. The knowledge of immunology, the ability to deploy that knowledge for patients at risk for breast cancer is here, and there’s a great amount of work. BCRF is leading that in terms of supporting any number of us who are thinking about these ideas. To me, it’s a super exciting possibility that we would have a vaccine to prevent cancer in addition to treating it as well.

Dr. Larry Norton: Thank you. It’s a great way to end the symposium, which we have to end on the future note of the fact that the future actually does look bright even in the area of prevention as well as everything else we’ve talked about. I just want to thank all the panelists, thank my co-moderator, Judy, and thank all of you for being here.

Many extraordinary new treatments, diagnostic tests, and procedures for breast cancer patients have been introduced in the past decade—and more are needed and sure to come.

But even with such revolutionary science, identifying ways to improve cancer care delivery, quality of care, and quality of life for patients and thrivers remains a significant concern. And that’s exactly what Dr. Dawn Hershman is working to improve.

A BCRF Investigator since 2008, Dr. Hershman brings a dynamic blend of science, psychology, theology, philosophy, and even public policy to her work. This research centers on improving cancer care delivery and health equity—from reducing treatment side effects to improving patients’ ability to follow their treatment plans.

Dr. Hershman has published more than 250 scientific articles and has received numerous awards, including being named to the most recent Giants of Cancer Care class. Dr. Hershman is professor of medicine and epidemiology and director of breast oncology at the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center.

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Read the transcript below: 

Chris Riback: Dr. Hershman, thanks for joining. I appreciate your time.

Dr. Dawn Hershman: Yes, thanks for having me.

Chris Riback: So when many of us think about breast cancer, we think about the worrying tests. We think about the treatment or the procedures. You think about all that but you also think about the quality of the lives of patients during and after breast cancer care, improving cancer care delivery and health equity treatment. Why is that where your focus goes?

Dr. Dawn Hershman: Yes, so very early in my career, it became very apparent to me that we had made tremendous strides in understanding better treatments, that it really had a big impact on improving outcomes of patients with breast cancer, but not everybody got them, not everybody accepted them, not everybody completed them. And there are a whole host of reasons why, and so it really made it clear to me that if I could make improvements in the treatments that work, if I could get patients better treatment that work, I could really have a big impact in terms of population survival. And who are the patients that are less likely to get some of the best treatments, the treatments that we know work?

Well, patients that maybe are less educated or have less access to go to one of the top five medical centers or patients that live in poverty and have competing interests for their time, or patients that just have a lot of other medical conditions. And so I started to investigate what are the factors that’s stopping people from getting the treatment and became pretty clear that a lot of it was a fear of side effects or development of side effects. So that was sort of the push and it’s taken me in a lot of different directions. What are the various different side effects out there? And what are interventions that can maybe lower side effects to get them through their treatment?

It’s helped me focused on things related to adherence. How do I keep patients on their medications and what are factors that interfere? And so we’ve done a lot of work looking at financial factors and co-payments and insurance status and how all that financial toxicity can impact treatment. We’ve looked at beliefs and persistent symptoms after treatment and how to make sure that patients [and] all of their quality of life needs are addressed during their treatment and after, and it’s helped us look at the ways policy decisions affect patients, whether it’s related to pain medication, or whether it’s related to issues related to reimbursement of oral medications or prior authorizations and how all those things can affect the quality of treatment that patients get. What started out as one thing sort of turned into many.

Chris Riback: Yes. It doesn’t sound like your life is complicated at all. I think your new business card reads scientist, psychiatrist, theologist, philosopher, and public policy expert. There’s no problem.

Dr. Dawn Hershman: Yes, no. No problem at all.

Chris Riback: It’s so interesting to hear you outline that kind of trifecta of challenges that you said at the beginning, the barriers to folks getting the medication or treatment, accepting the treatment and completing the treatment and in researching and the different impacts along each area, whether that’s socioeconomic class, education, fear, understanding, maybe other areas of support in terms of completing them.

In researching for this conversation, I saw that you were named last September to the Giants of Cancer Care class of 2021. Now, I know you have had a lot of honors in your career, but being a giant is pretty cool. I’m sure you would agree?

Dr. Dawn Hershman: I got ribbed a lot by my family for that.

Chris Riback: I would hope so. I’d be very disappointed if you hadn’t. And there’s another one to add to your business card, there’s giant. But I also read a quote of yours about that, which was, and this is you talking, “Figuring out how to keep patients on their treatment longer can have as big of an impact on patient survival as discovering a new drug.” That’s a powerful statement. And in reading some of your work, I just couldn’t believe that one of the major challenges is just ensuring that people actually take their medication.

Dr. Dawn Hershman: I think it was said best by C. Everett Koop, right? And he said, “Medicines don’t work in patients that don’t take them.” So we can spend a lot of time coming up with new treatments and new ways of giving it and combinations of treatment. But if a patient doesn’t take it, then we haven’t actualized the potential of that medication. And one of the things that’s so clear is that when we think of survival, we have to think not only of the breast cancer that we’re trying to treat and the patient, we have to think about all the other medications that they’re taking. And there are other comorbid conditions.

Patients don’t come to us with just one thing. They come to us with many things. And one of the things that we found is that when a woman’s diagnosed with breast cancer, they stop taking their high blood pressure medicines, their cholesterol medicine, sometimes they stop seeing all their other providers, because they’re just so focused on their breast cancer, for good reason. But if we cure them of their breast cancer, but they die of heart disease because we haven’t paid attention to all of these other things, then we haven’t made as big of an impact as we think we have.

Chris Riback: How do you balance your focus on root causes versus mitigation?

Dr. Dawn Hershman: Oh, that’s a great question. I mean, you have to understand in great detail what the root causes are to develop a strategy for mitigation. We live in a complicated world and root factors are sort of always shifting. And sometimes trying to come up with an intervention strategy maybe works for a short period of time, but doesn’t work for a long time. We live in this great world right now where we have all of these electronic mechanisms that are fingertips to help us enhance communication with our patients, communication with other providers, communication with pharmacies and other parts of the healthcare system that haven’t been really well tapped into. And I think if we can work with engineers and behavioral scientists and people with expertise in behavioral economics, we can use these new tools to help us, help our patients mitigate the barriers to whatever the problem is for them, because this is certainly no one size fits all kind intervention.

Chris Riback: And I want to ask you about that because my belief is that you are either starting or planning to start some study around the potential impact of integrating electronics and digital devices into communication. And having listened to what you said up to this point, it does seem clear why you would be advancing that, bringing all of those different hats that you wear together. But before I get to that, I will say, doctor, you do seem to practice what you preach. You have a not-uninteresting Twitter feed, which covers a lot of different areas. And one of them is you have reposted a few of the posts from the new New York City mayor, Eric Adams. And let’s just be clear, these are not political posts, but they all have to do with various healthy eating programs. Talk to me is that a personal interest, medical interest or both?

Dr. Dawn Hershman: Well, so if we want people to have better health outcomes, then we need to address all the factors that are known to affect patient’s longevity on every level and risk mitigation. So we know that diet and obesity and exercise increases the risk for developing breast cancer. And if we want to prevent it, we have to have good strategies in place that are accessible to everybody. And that start at with really young kids so that we can develop good strategies and for so long I think our policies haven’t really addressed the importance of prevention. And so I really am thrilled when there are public policies in place that address these issues.

Chris Riback: It makes sense. What is your comprehensive multidisciplinary program? How does it work and how have you developed it over the years?

Dr. Dawn Hershman: Yes, so I think the best research comes from really listening to stakeholders from all different types of backgrounds and I’m so privileged to work at an institution that has an amazing school of public health and great basic scientists and amazing clinicians, but also to work in New York City and really with BCRF because so many of my collaborators are other BCRF awardees with different expertise, expertise in community health and behavior and epidemiology and data science. And sometimes by taking all of these really smart people and putting them together, you can solve problems in a more creative way. And it’s the creative process that gets me super excited about being able to do new things.

Chris Riback: Let’s talk about some of your current studies on issues related to quality of life in the treatment of side effects including chemotherapy-induced peripheral neuropathy, a common side effect of a class of drugs called taxanes. Pain management for patients with metastatic breast cancer, chemotherapy-induced hypoglycemia, and more, what is the status of those studies, and where are you with them?

Dr. Dawn Hershman: Yes, so we have looked at a whole variety of ways of mitigating short and long-term side effects of treatment. And many have been quite successful in terms of reducing pain that comes from some of the aromatase inhibitors. We now are launching a large project looking at various different types of compression and cold gloves to the prevent the neuropathy that develops from chemotherapy to understand we have studies that suggest that patients sugars, for example, go way up during their treatment because of the steroids that we give and that may actually make their neuropathy worse. So it may even be that controlling their glucose during their treatment helps reduce some of these side effects.

We’ve been working a lot with pain medication and really doing a deep dive to understand what makes people stay on pain medications for too long, or, what stops them from taking pain medicine when they have pain and how can we best control pain in our patients. And we have a device that’s been very successful at helping patients manage their pain because it works through an app. But more importantly, it gives them an opportunity to send their medicines back when they’re done. And we’ve been able to get a lot of opiates off the shelves by using this device and returning it to the pharmacy.

Chris Riback: Yes. Pain management is such a complicated area. I know, I mean on the one hand, is so important because the advancement of pain must stand in the way of all of those other goals that you talked about, accepting medications, completing treatment, pain must get in the way at the same time, we all have followed the news of some of the concerns. In my understanding though, perhaps your approach to pain management involves medication, you just described it, but it seems fairly holistic. It seems to go beyond just medication. Is that accurate?

Dr. Dawn Hershman: Oh, yes. We have looked at a variety of different strategies, including acupuncture. We have several studies that have looked at acupuncture, which is extremely effective at reducing pain. And I think underutilized, mostly because of access-related issues and reimbursement-related issues. So we hope that the world is opening their eyes. We’re seeing more patients’ insurance plans covering it. Sometimes working with various organizations to try to figure out how to make it acceptable and widespread. So, people would much rather go to six sessions of acupuncture than to take an opiate. We need to change our reimbursement and our policies around that.

Chris Riback: That’s a whole other conversation that I’m sure you have maybe a couple of points of view on and certainly must create some angst and frustration when you see opportunities available for patients that you are caring for. But we’ll hold that for another conversation. For this one, the other study. What state are you at right now in terms of testing new electronic technologies to improve the patient-provider communication and enhanced pain management?

Dr. Dawn Hershman: Yes. Well, maybe I could tell you a little bit about this large initiative that we have, it’s a large study that we’re just undertaking that uses a variety of different tools to enhance patient-provider communication.

Chris Riback: Yes, please.

Dr. Dawn Hershman: And it sort of focuses on chronic medication adherence, which is a huge problem in medicine. It results in excess death, excess hospitalizations, emergency room visits, enormous like wasted cost to the healthcare system, and poor outcomes. And we know probably globally about two-thirds of patients that are on multiple medications, have of some type of non-adherence non-compliance or problems with their medication. We just did, also with help from BCRF, an intervention focused on video pharmacy visits, and found that like 90 percent of patients’ medications in the chart were different than what they thought they were supposed to be taking.

And that about half of patients, especially with advanced cancer were on two medications that interact with each other. So we’re using video visit technology, EHR alerts, and feedback and communications with healthcare providers, with pharmacies, when patients don’t fill their prescriptions to alert providers and patients and caregivers, and then apps to help remind patients when they’re supposed to take their medication. Trying to come up with solutions so when they have a problem that we can also connect them with social services to help resolve that problem in terms of getting the medications. So trying to think of all the different things that are out there and use them all together to improve the way we deliver oral medications.

Chris Riback: Yes. An incredible opportunity. Also raises other challenges around who has devices, who has bandwidth, internet access, all of that. Let me ask about you, how did you get into this? And I mean, going back, where did you grow up? Was it always science for you? Did you ever have a vision that perhaps you were going to be a fiction novelist or world-class skier or anything else? Or was it science, science, science?

Dr. Dawn Hershman: No, actually, my mother is an artist, and never in my wildest dreams growing up did I ever think I was going to end up as a physician or a scientist or as a researcher. I didn’t really know what my path was going to be. And I was lucky to be able to go to college with an open mind. And actually, it wasn’t until my senior year in college where I took a bio-psychology class, and I really loved it. And I ended up doing work-study as a research assistant. And when I graduated, I worked as a study coordinator on clinical trials and was encouraged to try. I started to see other physicians and at first, I thought, oh, I’m not smart enough to do that.

But actually, my husband now was like, “Just take the classes, just see how you do.” So I took classes at night when I was working and was like, “Oh, I can do this. This is really cool.” And developed that passion and went back to medical school after working as a study coordinator for a few years. And I think that experience of sort of discovering it, discovering that it’s actually super creative—science and medicine—and my husband’s a documentary film editor and a filmmaker, and my mother, as I said before as an artist. Like I’ve always felt like an outsider a little bit when I took this path. And I guess I realized that this is a super creative path too.

I feel so lucky because one of the greatest things about what we do is one, working with amazing patients and being inspired every day by the people that we see. I always say that if I didn’t take care of people with breast cancer, I would not have a single idea because every time I’m in clinic, another idea pops into my head about how we could be doing things better. But also to be able to work with so many other creative and interesting passionate people, and importantly, to be able to mentor the next generation of junior investigators. When you see somebody get their first grant or their first paper in and how excited it is they are about it. It’s a total rush. And so I think that’s what keeps us all going when things aren’t so easy.

Chris Riback: That comes across and what you described at the outset in that. We were kidding a little bit about the range of roles that seems you play and how long your business card needs to be. It makes sense in listening to your background, the mix of right and left brain, front and back brain probably too, all comes together for holistic care. To close out, how would you describe the role that BCRF has played in your research?

Dr. Dawn Hershman: I feel like I’ve been part of the BCRF family in one way or another my whole career. And it’s important in so many ways because one, it allows you to really be creative. Like, as I was saying before, the best part about being able to both see patients and do research is have a good idea, develop it and act in the moment. And the process we have is like you have an idea and then four years later you start the project. And because of this model where they fund people who have a track record and are creative and productive, that I have been able to leverage the funding a gazillion times over in both being able to have my junior investigators go on to get career development grants, me being able to get on larger trials and larger studies done using that initial work that we do in terms of developing an idea or an intervention through BCRF.

But it’s also like introduced me to this community. And when I look at the list, I’m like, “Oh, I’m friends with her, I’m friends with her. I collaborate with her. I collaborate with him, and he’s a good friend.” It’s like over the time you become a family and that’s an amazing thing.

Chris Riback: That’s terrific. And it’s very nice of BCRF to have put together a collection of your best friends.

Dr. Dawn Hershman: Right. Just for me.

Chris Riback: Just for you. It’s very, very kind. Dr. Hershman, thank you. Thank you for the work that you do and thank you for taking the time today.

Dr. Dawn Hershman: Absolutely.

We all know the saying: The apple doesn’t fall far from the tree. As the son of a dentist and nephew of a doctor, it’s no surprise then that Dr. Hy Muss ended up in the medical profession. Nor is his empathetic style of care which seems to emanate from his upbringing as well.

What might have been unexpected, however, was his area of focus. Unexpected because his specialty, geriatric oncology, was in its infancy when Dr. Muss began his career. Thanks to Dr. Muss and others, much has been learned about breast cancer in elderly people—and there’s still much more to uncover.

A BCRF investigator since 2000, Dr. Muss is professor of medicine at the University of North Carolina School of Medicine and director of the Geriatric Oncology Program at the UNC Lineberger Comprehensive Cancer Center. Dr. Muss has devoted his career to breast cancer research—with major interests in both early and late stages of the disease, treatment outcomes, and care for older women with breast cancer. He also has a major interest in biomarkers of aging and how they might predict survival and treatment response. 

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Read the transcript below: 

Chris Riback: Dr. Muss, thank you for joining. I appreciate your time.

Dr. Hy Muss: My pleasure. It’s great to be here.

Chris Riback: I want to get into, of course, your science and approach to care, but in researching you I’ve got to say it became obvious where I had to start. What does it mean to be a real Brooklyn boy? And while they can take the boy out of Brooklyn, you’re, I assume, in North Carolina right now where you work. Doctor, can they ever take the Brooklyn out of the boy?

Dr. Hy Muss: Never, never. So, I’ve lived in North Carolina a long time, but I’ve heard myself being referred to as the guy with the New York accent that’ll take care of you. So, it never leaves. And I’m very proud of it.

Chris Riback: I would imagine that you are.

Dr. Hy Muss: Yes, I’m proud of it.

Chris Riback: Why would they ever want to take the Brooklyn out of the boy?

Dr. Hy Muss: Well, there are people that try to move up in life and don’t want to show their roots. I think more people like me, we’re very proud of where we grew up.

Chris Riback: True.

Dr. Hy Muss: One of the great cities of the world before they built the Brooklyn Bridge. So very proud of it.

Chris Riback: Yes. And the second item that struck me, you may not read your own reviews online and I hope you don’t mind, but I did. And here’s just a little bit of what your patients say. “Dr. Muss is off the charts wonderful!!!! Very empathetic and willing to listen, conveys his compassion for situations in an effective manner. Dr. Muss is outstanding and kind and professional.” “I appreciate Dr. Muss’s warm and kind demeanor so much. He is an exceptional physician. I am grateful he was in charge of my care. He is an amazing man.” Now first, just for the record, you don’t fill those out yourself, correct?

Dr. Hy Muss: I don’t, nor does my mother.

Chris Riback: I understand the desire that she would have to do so, but those obviously are powerful and meaningful. Why are empathy and compassion seemingly as much a part of your approach as is scientific or medical expertise?

Dr. Hy Muss: Well, first, I’m very honored and flattered by the comments. They’re very lovely. Probably my upbringing, my parents were wonderful people. They welcomed everybody. My father was the neighborhood dentist. My uncle was the neighborhood GP. My mother lived in the same neighborhood. And I guess she was the therapist to half the neighborhood people when they had issues, but they were wonderful caring people. And I thought their style and how they lived their lives was important. And there are so many patients we have that are so sick, so afraid.

Most of us know the medicine. We know the statistics of the treatments, et cetera, but trying to get a patient comfortable, getting to know them. I often tell our residents, if you don’t know whether this patient has a dog, you’re not doing your job. And in this frenetic age, I think getting to know people and being kind makes you more effective. They’re more likely to take your advice, to trust you. And so I try to do that and give a little bit of me at the time. My heart’s on my sleeve. I’m a very easy read, but it kind of works for me. It’s not for everybody. And I think that resonates with some patients who are petrified of their diagnosis and want more than the treatment plan.

Chris Riback: Petrified is surely the right word for so many and helping them manage that component of their care. Listening to you is perhaps as much as the science in terms of importance, or certainly close. You may know that you’ve been called a triple threat, excelling in research, education, and the clinic. So let’s talk about the research if we could. I wanted to first understand geriatric oncology. Has that always been your focus and what drew you to it?

Dr. Hy Muss: So, it hasn’t always been my focus. I finished my fellowship a long time ago, 1974. And when I finished fellowship and went into academic oncology, which I’ve been in all my life and which has been just a great career choice for myself, no regrets, we treated all cancer. There weren’t specialists in leukemia and lymphoma. The tools were so marginal. It took a long time to make oncology a specialty. I took the second set of boards and that was because to become a medical specialty, I had to prove you could do things for patients, not just identify a disease. So I was in early, but as things evolved and treatment got better, surgery, radiation, chemotherapy, all the modalities got better, prevention, early diagnosis. You had to specialize to really be an academician, and that’s still true, more and more true today.

And it’s actually happening in the practice situation in the community where docs are taking little niches. So, I did all types of cancer over the years, got into breast cancer and then had the great experience of working with one of probably the planet’s great geriatricians, a guy named Bill Hazard, who’s emeritus professor at Wake Forest, who wrote the first textbook on geriatrics and who try to proselytize all [and] get us interested in geriatrics. So, a long story, but I wrote a paper with one of our residents, Kathy Christman. At that time, she’s a practicing oncologist, on older people treated with metastatic breast cancer. And at that time, many clinical trials excluded older people. They were written right into the criteria, but we did not. I had an incredible boss.

Now you can’t do that. That’s ageism. And this is 30, 40 years ago. Now it’s a popular term. Then no one knew what ageism was, but he did. And so, we included it and we showed that the older people derived similar benefit. They didn’t have profoundly different toxicity and they had the same response rates and survival. So we published that in JAMA. And all of a sudden, I had friends calling me about their mothers, grandmothers, and patients who were older. And I realized, I didn’t really know a lot about them. I wrote this paper, but I didn’t know a lot about caring for older people. And I got interested. I learned a lot. I had the opportunity of working with people nationally, like Harvey Cohen at Duke. We chaired a major committee and slowly morphed into geriatrics, especially when I learned the demographics. Right? So in the elevator, people say, how come you’re interested in that, Hy? And I’ll say, what’s the average age of cancer in the United States? When they watch TV and they see Brian Song and they’ll say 45. No, it’s 67.

So, as we get older, as an aging population, as we get older, your chances of getting cancer rise dramatically with age. And as we get an older population, there are more and more of these patients. And the challenge is they frequently come to your clinic with more than cancer. Now, there are 75-year-old tennis players, and there are 75-year-old people who are quite ill, not from their cancer frequently, but from diabetes, heart disease, and strokes. And the challenge is to sort out these people and identify the problems of the patient and take care of the cancer as well as the patient.

And sometimes the cancer, although the word is profoundly intimidating, is really not the patient’s problem. They can’t walk down the street without falling. So, I’ve slowly gotten interested in this. And as you may be aware, Medicare is a great service, but caring for older people in the United States is extremely difficult. We’re short of physicians, we’re short of geriatricians, et cetera. So, we’ve become interested in this field in trying to improve cancer care in older patients. And it’s a great challenge. And working with older people is a great reward.

Chris Riback: And I know from reading just a little bit about you, I believe that among your questions that you will ask a patient is can you walk to the end of the street or a lot of questions and investigation around mobility and frailty.

Dr. Hy Muss: Sure. I mean, when you take care of a patient today, we’re all specialists and we all have the patient’s records and know about the cancer. And so my style is with older people and with all patients is my first question is after I introduce myself and tell people what I do for a living is to say, tell me about yourself. I tell them, I know about your cancer. Tell me about yourself. What do you like to do? Are you working? Are you retired? Get to know people. And then as part of my evaluation, because that tells you a lot about people.

Chris Riback: Yes. Yes.

Dr. Hy Muss: I do a little what they call a geriatric assessment, which can be very formal, but it’s essentially knowing in an older person, can they care for themselves? Do they pay the bills? Are they a caregiver for their husband or wife, or are someone caring for them? Can they move the chair across the room? Do they have friends and social support? Are they eating enough? Most older people losing weight are not doing it because their cancer is spread. They’re doing it because they’ve lost the joy of eating and don’t have the same appetite. And so all these things come into caring for the older patient and frequently they trump the issues related to the cancer.

And what’s important about it is many of these issues are fixable. So in addition to your treating their breast cancer, which may have an excellent prognosis, you may send them to physical therapy so they don’t have a fall and break their hip and start on a very disastrous road. So geriatric oncology maybe is the consummate form of holistic medicine in that we’ve really got to know that whole patient, because there’s vast differences in health status, income, social support in older people. So you just can’t say she’s 75 and have an image in your mind, which most people do of maybe someone older, because they can be vastly different patients depending on their function, et cetera.

Chris Riback: So, I think I know what aging is, but what is molecular aging?

Dr. Hy Muss: Yes. So, one of the mysteries of biology, of life, is why do we age? Why is people hair going gray? Every organ system in our body, including yourself. I hate to tell you this.

Chris Riback: Only half as much as I hate to hear it.

Dr. Hy Muss: After around 30 or 40 is declining. We’re losing little air sacks in our lungs. Our kidneys can’t filter as much blood. Our liver isn’t efficient at building proteins. Our heart doesn’t pump quite as strongly. We’re losing brain cells. Nothing to be afraid of. We have a lot of reserve, but we slowly lose this. So why does this happen? And one of the things is in our environment, even oxygen causes little damage to a lot of the cells in our body, subtle damage that accumulates. And for instance, take a liver cell. So over the years, the liver cell may be damaged by oxidation, by chemicals coming into it. And what the cell does is it slowly changes to a cell that can’t divide and replenish itself, but it doesn’t die. It’s what we call senescent, the terrible term, because we call some old people senescent. I hate it.

They [the cells] can’t divide, but they don’t die. And they actually make dangerous little chemicals, inflammatory and other proteins that actually can predispose people to cancer. And that may be why cancer is more common as we get older, because we accumulate all these inflammatory and other factors that flow through our circulation all through our body and increase our risk for virtually any type of cancer—[cancer] increases with age, from leukemia, breast cancer, colon cancer, cetera. So biologic aging is this process where cells go from vigorous cells that can divide and replenish organ systems to cells that don’t divide well, but are not dying and make actually bad things for us. And that varies too. But the interest is that may help us predict side effects of drugs, may help us predict in the future who’s likely to be very robust and who’s likely to be frail.

Now we don’t know all of this yet, but it’s a hot area and there’s more and more wonderful scientists in the laboratory, social science, medical care involved in trying to figure out this process. So biologic aging is really real. It’s why we change as humans, but the major causes, can we reverse it? Billion dollar business, looking for drugs to keep us young, right? Fountain of youth. Hence Florida, right? Ponce Deleon. So, we’re still looking and there’s a lot of wonderful laboratory work here too and I would say the focus of people like me is not to make people immortal, that’s not going to happen. That might be a curse, but to live the best life you can for as long as possible in the best health.

Because if everybody lived to 85, it would be much different if people lived to 85 with a great life between 65 and 85 and vigorous and could do things or sitting in a wheelchair watching television all day and not being able to take advantage of life. So, the endpoint might be the same, but the quality of life would be vastly different. So that’s things we’re very, very interested in seeing if we can affect.

Chris Riback: And on the oncology front, how does chemotherapy induce the biological aging that you were just discussing? How does that science work?

Dr. Hy Muss: So, the best example, how do we know that? What’s the best proof? It’s children. So, childhood cancer in this country is one of the great achievements of oncology of cancer care because we’re curing so many children with cancer. Leukemias that took the lives of young children in weeks to months are now cured, but there’s a price that many of these young adolescents and children pay. And that is by the time they’re 35, they actually have the disease spectrum of 65-year-old adults. And it’s not because the cancer is grown back. It’s because they have heart disease. They have developed second cancers different than the first.

And so the mortality rates go up and they have a lot of serious illness and they get frail. And I’ve worked with this with one of my colleagues. That’s the best evidence. And there’s also things like evidence in when we’ve given women chemotherapy and measuring the oxygen, they can take out of their lungs. Like Lance Armstrong took all that oxygen out. He was a great biker. And we found that if you give women chemotherapy that if you have two 65-year-old women and one had chemotherapy and one didn’t, the 65-year-old woman will have the oxygen extraction of really a 75-year-old woman. She’s aged 10 years. And the only explanations we have are the chemotherapy. And then there’s been our work, which couldn’t have been done without BCRF to look at another marker of aging, a gene called p16.

Chris Riback: Yes. I wanted to ask you about the p16 marker.

Dr. Hy Muss: That as we age goes up, the expression of this gene goes up and what it does is it codes for a little chemical that stops our cells from dividing. These changes in the gene, you see are responsible for the organ declines in every organ of the body, whether it’s the kidney or lungs. And it’s probably true from the limited data we have in humans. So we measure this gene whose little protein, little chemical goes up dramatically as we age, makes our cells less able to divide, and we’re measuring them in the immune system.

One of the questions that we talked about earlier before this was, do we know the implications of that? We really don’t. It takes years to see these changes. You treat children with leukemia at ages 5, 10, and 15. You don’t see the changes till they’re 15, 20, or 30. We’re impatient populations. So we don’t know, but we’re very concerned that these changes may result in that 55-year-old women having much more serious illness, comorbidity, diabetes, heart disease, and lung disease, when they’re in their 70s, than a similar woman her age would have who didn’t have chemotherapy or breast cancer or other, and was shown it in other cancers too. So we are very excited about using that as a predictor of side effects and seeing if we can accurately predict certain side effects, could we do interventions ahead of time to prevent them? And probably we can get to it later.

The main one we’re interested in now is what we call peripheral neuropathy. A lot of chemotherapy drugs, taxine drugs, which are widely used in breast cancer, are among the most effective drugs in breast cancer, both in early and late breast cancer, those drugs damage the little nerves that go to our fingers, toes, and can cause numbness, tingling, pain. If it’s very bad, it can affect your ability to walk, open a jar of ketchup, can have a profound [effect]. And it affects a lot of people. And certainly, for certain occupations, it can be terrible. Like if you’re a violinist or seamstress. And so we’ve actually through BCRF help, been able to show we can predict this pretty accurately. And we’ve actually got a National Institute of Health-funded study now to verify it. And so we’re excited as a predictive factor.

And then we’re also looking to see if we can predict other chronic diseases as you age, like what’s your risk of heart disease or diabetes. That’s trickier because we take care of cancer patients and they get out five or 10 years. We discharge them to their family doctors, but we may need to think about following these people much longer over the years to see if there are problems. And if there are, could our research have predicted who will get them? So, studying this gene may open a lot of opportunity to do different things for different people, prevent side effects in the short run, by identifying people at high risk, and using an intervention that may be helpful.

And then in the long run by who’s going to get other serious other diseases of aging. And that’s very important because most women with breast cancer today fortunately are cured [after] their treatment, but we’re treating them very aggressively. And if they get chemotherapy and perhaps lots that they need, large amounts of radiation, et cetera, that may have adverse effects down the road. And so we’re very interested in learning more about that.

Chris Riback: I’m sure that you are. On this point of studying chemotherapy and the effects. So you helped publish in 2009—I think it was in the New England Journal of Medicine—the results of the first chemotherapy trial in older patients with early-stage breast cancer. Now, earlier in this conversation, you discussed how you were at the very beginning stages of I guess geriatric oncology, and that predated this 2009 study. But I was shocked that it took until 2009 before somebody thought to do a chemotherapy trial on older patients with early-stage breast cancer?

Dr. Hy Muss: Yes. Well, our field is very new. I don’t know if there are 100 geriatric oncologists in the United States now. But in the early days of clinical trials, older people were frequently excluded, was a paternalistic approach, which should have never happened, but it did. It was ageism. And people didn’t appreciate the demographics. So there were virtually no trials focused on older people. And a lot of the data that we used were done on younger people, people in their 40s, 50s, maybe early 60s. And so their tolerance of chemotherapy may not have been representative of older people. And so fortunately with the support of my colleagues, Larry Norton, Cliff Hudis, Eric Weiner, great people, the Alliance, Rich, really terrific people, we wrote this study and we published it in 2009, but we started this study in 2000.

Chris Riback: Wow.

Dr. Hy Muss: It was nothing then. And we had to convince the NCI, which were very gracious, good people that it was worth doing. Because if you looked at clinical trials, even if they didn’t have an upper age, they were like two people, 70 and docs wanted know if I give Mary Smith who’s 76 chemotherapy, is it going to be an overwhelming problem for her? So we did this study, it was a national study. It took us a long time to accrue. And we found out that it was a group of women. In retrospect, there probably women who had triple-negative breast cancer who were older, who derived the greatest benefit. At that time, we didn’t know a lot about triple-negative breast cancer, but in retrospect, that’s probably what we showed. There certainly may have been some patients with hormone receptor-positive. There certainly are who derived benefit from chemotherapy, but that was the first seminal study.

And they were all over 65 and we had great support nationally. And we were very proud of it. And in fact, at the recent ASCO meetings is one of the few other studies. Most studies in this area, a lot were started. They weren’t completed. It was hard to randomize people. We had to randomized women to a chemotherapy oral form, a single pill versus IV chemotherapy. So those women were incredible to agree to this. And a lot of other people have tried this and not been as successful, but kudos to our French colleagues, Dr. Etienne Brain, and his group, for just at ASCO now publishing a very large study and kind of showing sadly that at least using the technology they did to select patients, the chemotherapy had little to no benefit when added to the endocrine therapy, to the hormonal like therapy, Tamoxifen in older patients, not a very good study.

There’ll be a lot of discussion. It doesn’t mean there’s no benefit for chemotherapy as a blanket statement in that group of people. But in our study, we included other people. So it was a little different, but it was terrific. And even now, as we speak worldwide, we don’t have more than a handful of studies focused on older people. There are some in leukemia where we know the biology is a lot different than older people than younger, but in breast cancer, colorectal cancer, lung cancers, we just don’t have as much. But people are coming around. The FDA is pushing pharma to include older patients and encourage them on trials. The National Cancer Institute has been wonderful and the National Institute of Aging, but it’s still been very, very hard to do to get these older people on trials. So we’re proud of the trial, but we’d like to see many more of them, but it’s been difficult.

Chris Riback: And that’s what I was going to ask you. What would you really like to know next?

Dr. Hy Muss: Well, I think it’s several things. I think from the tumor biology point of view, we’re learning a lot from people of all ages, but one of my interests is going to be are these biomarkers of aging? There’s a lot of interest in what we call bio clocks. As we age, our little methyl groups, little almost like hydrocarbon groups go onto our DNA and change the way it works and adds to our aging processes and developing other areas. There’s a lot of interest in that. And I think that’s a little bit different. That’s going to be focused on can we predict how certain people will do with certain treatments or without treatment? But I think one of the challenges now is there’s such an explosion of new drugs that affect the immune system, all the new immune inhibitors and all the new, exciting biologic agents.

There were some wonderful news for breast cancer patients from this year’s ASCO on drugs that attack the HER-2 gene, even if it’s not our standard definition—very exciting and wonderful work by Dr. Modi and her colleagues. Then the question is, do we know about older people? Is that 80-year-old person going to do as well? And so, what I’d like to see, and the National Clinical Trials Network, the NCORP [NCI Community Oncology Research Program] people have given support to the large groups to do studies of these drugs specifically in older patients. And it’s not to repeat the response rate, although that’s important because I think it’s going to be pretty similar. It’s to look if the toxicity profiles are different. So, we can make sure that older people on this what appears to be a terrific new drug, trastuzumab-deruxtecan, do older people get more of these lung side effects than younger [people]?

You might have a trial with 1,000 patients in it, but when you parse it out and you get people over 75 and 80, you end up with a handful of people and it’s not good enough to really get a good idea of the confidence you can have in the risk of these side effects. So, I think a lot of the research is going to have to focus on older people who still don’t get on these trials and very little headway, very little headway, and getting more older people on NCI trials and look at the pharma data. The FDA has done a beautiful drug trying to push to do it, but it’s difficult to do it because pharma has developed some great drugs, but no CEO wants to go in on Monday, say, ‘I put a lot of older people on the drug, and they didn’t do too well.’

Chris Riback: No, I’m sure not.

Dr. Hy Muss: Not going to do too well on the Dow that day. So I think we’re going to have to do them and they’re very important and we’re going to have to take the best treatments, not just in breast, but in all the cancers and really focus in on older people. And in breast, a lot of these treatments that we’re doing today, adding these cyclin-dependent kinase inhibitors to preventive therapy, adjuvant therapy, drugs that have not just costs, but monetary costs, but a lot of potential side effects, very little is known about the older patients. And I think we need to focus on carving out trials specifically for those older people.

So, when they come into our office and say you know Dr. Muss, I’m 78. I’m a little shaky on my feet. Is this drug going to have really bad side effects in me that I’ll be able to look that person in the eye and say we’ve studied a group of people like you, and here’s what we found. Yes. It was a little worse, but it may be worth trying it or not a good idea and I think that’s what we need to be focusing on.

Chris Riback: Yes. What a call to action and complicated call to action to generate studies on geriatrics. And I can only imagine you’ve outlined some of the issues. I can only imagine how complicated it is from companies to agencies to support it, to the patients themselves who may be tired and have other things going on and may not feel like participating in a study at 75 or 80 years old is kind of what they should be doing. And I could almost imagine an argument of how meaningful participation in such work could be.

Dr. Hy Muss: Absolutely. We did a study in the old CALGB [Cancer and Leukemia Group B] group. It was one of the first studies we did in geriatrics. And we looked at institutions that were part of the group. And we looked at what trials they had available in their institutions. And these were top-quality academic centers. I’m not going to name them. But when we looked, all these patients were eligible for a clinical trial. But when we looked how many patients were offered it by age, we found out that if you were less than 65, about half the patients were offered it. That’s bad enough because it meant that people were too busy or didn’t think of it or whatever. But when you looked at people 65 and older, it was only 25 or 30 percent.

Chris Riback: Wow.

Dr. Hy Muss: So, there was an intrinsic ageism because all these patients were eligible. And then we said, if you offered the patient the trial, how many accepted? And it was the same for older and younger people. It was about half. So, if you spent the time discussing the trial with the older patient, they were as likely to participate as the younger patient. Now there’s a bias in there. We didn’t offer it to all the patients. But those that we did and there’s been other work like this, and it’s very, very important. And it takes longer to explain things to older people. In this country, older people tend not to have the education of younger people, although we’re so numerically illiterate as a culture. I’m not sure that all matters, but explaining it, people are scared of placebos and it takes time to do it.

And of course, with older people, you’ve got to get their caregiver or family involved. They got to be part of the team. Everybody’s got to be in sync and understand about it. And so we’re working on it, but it’s not like in the United States, we’re getting more and more funds to screen older people and do things. I love to see it, but it’s going to take a while. We need a few more Claude Peppers [in government] and old committee chairman with power to put a lot of money in aging research, but it’s a challenge. And it’s a challenge for all the doctors and nurses and research associates, trying to get these patients on trial, irrespective of the type of cancer. Takes a lot of work. A lot of logistics. Caregivers got to be involved, but we’re not going to give up.

Chris Riback: Understood and quickly to finish out. How would you characterize, what role has BCRF played in your research?

Dr. Hy Muss: Well, BCRF has really been instrumental. We wouldn’t be having this conversation if it weren’t for BCRF. So, I’ve had the continued good fortune of being funded, of knowing the lovely, elegant, amazing Evelyn Lauder, and working with Larry Norton and other people who built this from the ground up. This organization’s philosophy has been to support investigators who have done some things but give them money to do new and exciting things. And I think our research in looking at how the biology of aging affects cancer care and older women with breast cancer, and we’ve looked at side effects and patient-reported outcomes, et cetera, I could never have done it without BCRF. And it has led to some lovely, lovely funded NIH grants. I’ve had the opportunity of working with Ned Sharpless, our prior director, who’s really taught me the biology of aging.

But without the BCRF providing those hard dollars to do these studies because they’re not like drug A, and we’re going to get a new drug that’s going to cure everybody. They’re much more translationally based from the lab to the clinic, than learn about patients and bring it back to the lab. Couldn’t do it without BCRF. And so they’ve enabled us to do this, to look at new little nuances with continued funding to build on these studies. And I think in our case, we’ve been able to get federal and other grants to actually leverage their wonderful support, but it wouldn’t be possible. Wouldn’t be possible.

Chris Riback: Dr. Muss, thank you. Thank you for your time. Thank you for what you do with patients, both those that are your patients and those who are not every day.

Dr. Hy Muss: Well, it’s my pleasure to have been here to discuss this. Thanks for asking me. And as always, I appreciate the BCRF support and interest in what we’re doing. Thank you so much.

How do you measure quality of life? As researchers across fields discover new drug therapies or disease prevention—in breast cancer as well as other fields—science finds innumerable ways to measure physical results. But what about the social, behavioral, and psychological aspects of cancer care?

As importantly: How should medical providers discuss such realities with patients—to help them understand the important benefits, but also the emotional and physical challenges that can come with some therapies and preventions.

This is just one area of extraordinary impact that Professor Dame Lesley Fallowfield has made in medicine. Dame Lesley is professor of psycho-oncology at Brighton & Sussex Medical School at the University of Sussex where she is director of the Sussex Health Outcomes Research & Education in Cancer group.  

She has been a BCRF Investigator since 2016—the same year she was made a Dame Commander of the Order of the British Empire by Queen Elizabeth II for services to psycho-oncology.

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Read the transcript below:  

Chris Riback: Dame Lesley, thank you for joining. I appreciate your time.

Lesley Fallowfield: My pleasure. Glad to be with you.

Chris Riback: So, let’s start at the very top. What is psycho-oncology?

Lesley Fallowfield: Yes, sounds a bit sinister, doesn’t it? Like a vision from the shower scene in “Psycho.”  Essentially, it’s looking at the social, behavioral, psychological aspects of cancer care. So, that embraces a whole range of things. It can be anything from support for patients, educational training of healthcare professionals who deal with cancer patients, to actually looking at ways to measure quality of life in big clinical cancer trials, for example.

Chris Riback: And I wanted to ask you about that and quality of life. It is such a prime overlay of so much of your life’s work. And for us outsiders, we think of healthcare professionals in a clichéd sense, I would say. It focused primarily on physical health, is the patient sick? Is the patient healthy? Will she live or not? Why were you inspired to think and act so seriously in the area of quality of life? And to pick up on what you just said a moment ago, how do you measure that?

Lesley Fallowfield: Okay, well, that’s quite a big question to unpack. I mean, if we start at the very beginning, I used to be actually a visual scientist and I was developing ways to measure the integrity of the optic nerve in patients who’d got demyelinating diseases like multiple sclerosis because they started to have all sorts of strange visual problems that clinical tasks couldn’t pick up. So, I developed some ways to actually measure the things that patients were complaining of. So, that was where my career was focused. And sadly, my very closest friend who used to help me with the school, run with the kids, she was only 34 and she developed acute myeloid leukemia. And she had one of the first bone marrow transplants and sadly died of graft-versus-host disease. Now, when she was in hospital suffering the appalling sort of problems that you get with that, she looked up at me and she said, “You’re meant to be so clever. Why don’t you measure something important?”

 And I said, “Well, I am measuring things that are important.” I said, “What do you mean?” And she said, “Well, why people do things like this to you without really telling you what could happen? Why can’t you measure the benefits of actually doing things like that with so many serious side effects?” And she died about two weeks later, and I thought very long and hard about it and read an article by a breast cancer surgeon, in fact, saying that he thought the psychological aspects of breast cancer were poorly understood. So, I just phoned him up and I said, “Give me a job. I want to come.” And he said, “Well, you don’t know anything about cancer.”

And I said, “So teach me.” I said, “I know how to measure difficult things. I know how to measure things that people think you can’t measure. And I’ll find someone in the world who’ll give me a job because I promised my friend.” And so that really is the background. I am a scientist. I had a degree in experimental psychology in neuroscience, but I’ve applied all of that work into my psycho-oncology and certainly measuring difficult things has been a major part of that.

Chris Riback: Well, I don’t know how anyone could have withstood the pitch that you gave, “I made a promise to my friend,” and obviously that person didn’t resist your pitch. It’s also just so striking and sad to hear. So that wasn’t even being considered, measured at that point, as your friend was going through her cancer treatment?

Lesley Fallowfield: I mean, there’s several ways of looking at this, isn’t there? I mean, obviously when people have life-threatening disease, many people, not just the healthcare professionals, families as well, are so focused on survival, but of course, survival at any cost isn’t always very worthwhile. We need to think about the quality of survival and that’s actually as relevant now as it was then. Certainly in, we’re talking about 1984, I’m very old, I don’t forget, in 1984, if you looked at a literature search then, you’d probably come up with about two or three papers that actually mentioned phrases like quality of life. And so, it’s been a long, hard road to actually get to the stage now where people do accept that it is important. I mean, one of the things that has happened over the last a couple of decades, really, I think I’d say, is that, because of our improved understanding of the molecular biology that underpins a lot of the development of cancers, we’ve seen some incredible therapeutic advances in new and different treatments.

That actually means that many patients have got a realistic prospect of cure or living much longer with their disease and hopefully living well. And a lot of these advances have been because of the fantastic researchers that are funded by BCRF. So, thanks to all the people who make donations because they really have made a difference. But if we come back to the, if you like, quality of survival, nothing actually comes without cost. And I don’t mean financial cost, I mean toxicities and impact therefore on activities of daily living that make life worthwhile. And often it is baby steps in terms of improvements, but over the years this builds up, if you’ve got a new drug or a new procedure that can add a few extra months or extra years of life, it’s so important to be absolutely clear about what the toxicities and downsides are. Not because we then stop actually giving people those beneficial and efficacious treatments, but so that we can work out what sorts of ameliorative interventions or supportive things we can put in place up front to help patients cope with the side effects.

So, if you think about it, I mean, if we look at metastatic breast cancer, for example, and we’ve seen some big changes there with sometimes people living with metastatic disease for many years, but a lot of these patients, of course, have other lives, other responsibilities that they want to fulfill. They wish to pick up the grandchildren from school so that their daughter can go back to work or maybe they want to look after a [a spouse or mother or father with dementia] or just play tennis and walk the dog. And if you’ve got, for example, horrible, chronic diarrhea or fatigue, you’re not going to be able to do any of those things. So, the question becomes well, do I want to live in this house-bound state because of the side effects of treatment or do I want to take another treatment, which might not extend my life quite as long, but would at least allow me the prospect of doing the things that make my life worthwhile? So that’s why we’re very focused now on the quality of survival, we certainly are doing great things about the quantity of life, but we’ve really got to do a lot more about the quality of life.

Chris Riback: Who are those conversations hardest for? I mean, I hear you talking about balance and balancing the toxicity versus quality and what you just said, the quantity versus the quality. Are those toughest for the patient? Are those toughest for the family? And what about the medical profession, how skilled or not skilled, generally speaking, do you find them at that?

Lesley Fallowfield: Well, that’s a question because we’re all different, aren’t we?

Chris Riback: Mm-hmm.

Lesley Fallowfield: We talk a lot now about shared decision-making so that no decisions about me without me, that patients and their families need to be an integral part of the decision-making about what to do next. That’s, of course, easier said than done really, because first of all, I mean, there’s several things, first of all, there’s the complexity of information giving about things and a lot of treatments, a lot of tests and everything, you need an undergraduate degree in, I don’t know, biology to understand some of it. So, putting complex information in front of a family and patient in understandable terms without being patronizing, of course, is a hard thing to do. And I think a lot of healthcare professionals really severely underestimate the literacy and numeracy levels of most of the general population, even people who are graduates struggle with probabilities and possibilities.

So that in itself is difficult enough, but then you have to, I think, layer into this problem in terms of communicating and having a genuine two-way exchange. The fact that healthcare professionals, not because they are bad people, they are good people fairly often, but they tend to talk up, for all sorts of reasons, the benefits, they’re very good at talking about the benefits of treatments, less competent and confident sometimes about talking about the downsides.

Now this is sometimes because you want to, it’s a hackneyed phrase, but you want to give patients hope, keep them optimistic. And that is, on one level, a good thing. But I think sometimes that the healthcare professionals themselves start to want to believe in the same sorts of miracles as do their patients. And then you’ve got an interesting exchange that goes on. So, when you’ve got a deeply anxious patient, perhaps with their relatives, desperate for positive news, healthcare professionals are human beings, too, they want to feed into that, they want to make that better, and so sometimes they over-egg the upside of things and underplay the downside of things. And I can see so easily how that happens. It’s really hard to be honest with people about therapeutic benefits versus the harms.

Chris Riback: So, you have just made clear for me, I came across one of your quotes where you stated that oncologists need to be aware of their own tolerance of uncertainty before discussing possible treatments. And I caught up on that phrase, “tolerance of uncertainty,” but I think you just described what you mean, didn’t you?

Lesley Fallowfield: Yes. I mean, maybe I could just explain it a little more in terms of some research that actually the BCRF funded us to do, which was absolutely fascinating. And in breast cancer, there’s a lot of effort now to deescalate treatment. And by that, that means not give patients treatments that really have little prospect of adding anything to cure or long-term survival. And we know from all sorts of different sorts of studies that not all women with early breast cancer need or should indeed even have chemotherapy. There are certain types of breast cancer [that are] treated well enough by surgery, radiotherapy, and endocrine treatment (hormone treatments). But, of course, it’s quite difficult to explain to a patient that we don’t always need to give you all the things that they’re expecting. Well, perhaps give them a better outcome. And so, there are these wonderful new tests called gene expression profiling tests, which basically can help determine whether or not a patient is at low risk of the cancer recurring, intermediate [risk], or high risk.

And so obviously the patient is at high risk, no question about it, they really should be offered chemo, but there’s a bigger question about the intermediate and low risk patients who probably are happier, better off not having the chemotherapy for no benefit. But if you’ve got a very anxious patient who has got a high intolerance of uncertainty and the doctor talking to her has a high intolerance of uncertainty themselves, and let’s say the score is intermediate or just on the cusp of being high, there’s no way that patient leaves the clinic without actually a prescription for chemotherapy.

Chris Riback: Because that’s certain. We know it’s going to happen there.

Lesley Fallowfield: Well, absolutely. It’s got nothing to do with the characteristics of the tumor and the results of the test. It’s got everything to do with the psychological disposition of the patient…

Chris Riback: Of both parties.

Lesley Fallowfield: The doctor talking to her.

Chris Riback: Fascinating.

Lesley Fallowfield: So, we ran all these courses where we develop lots of educational materials and we found that we could improve the doctors’ competence and self-confidence when they were talking with patients about different sorts of gene expression, risk of recurrence scores with different types of patients. So that was a really interesting study to do, because unless you give doctors some awareness of how these sorts of things, their own sorts of personality, types, attitudes, leak into the conversation, they don’t understand why sometimes patients make perhaps rather irrational decisions.

Chris Riback: That is such an interesting thing to hear as an outsider, because we think about that all the time in any conversation with a spouse, family, at work that one’s own psychology situation circumstances, learned experience, lived experience, will inevitably drive, influence, or inform any conversation that we have with someone. Particularly, I would think, the more difficult the topic, the more of those lived experiences and behaviors must form one’s own participation. But as a lay person, speaking for myself, we don’t think about that from a medical professional. We think that, of course, they’re in control of all of their faculties, medically, psychologically, emotionally, and what a fascinating way to view it and an important contribution.

Lesley Fallowfield: I think one of the problems, of course, is that medicine is not the exact science that we would like it to be.

Chris Riback: Indeed.

Lesley Fallowfield: And people don’t like ambiguity, particularly where you’ve got life threat involved. They really want a clear direction that this will help, this will not, and it’s just not quite as clear-cut as that. And I think that’s where the problem comes.

Chris Riback: Often life is not quite as clear-cut as that, unfortunately isn’t that, or it’s the reality, that’s what it is. Now, one of the things it seems that you are trying to do, in terms of helping the medical profession, helping healthcare understand those conversations, is really scale that ability, because as amazing as you might be, as incredible things as you might do, I’m willing to bet that you can only be in one place at one time. You haven’t quite figured out how to clone yourself. And so, the TRUSTING educational program that you are working on, could you tell me about that? What is it? What does it consist of? Why is it important? And if you could tie it in as well, I don’t know that it’s solely around, but I believe it’s around the idea of discussing genetic testing results. So, tell me please about TRUSTING.

Lesley Fallowfield: OK. So, TRUSTING is another educational program that we’re doing with BCRF backing, which I’m so grateful for. We spent a lot of time talking with women who are at high genetic risk of breast cancer. And as you’re well aware, you’ve got the BRCA1 or 2 gene mutation, you have a predisposition towards breast cancer, but other cancers as well, ovarian cancer, and [in] males in the family, prostate cancer. So, we were concerned about, particularly if you like, the celebrity effect of well-known individuals deciding to have prophylactic mastectomies, because they carry the BRCA gene. And lots of young women becoming very concerned about their risk because someone in the family had cancer. Now talking again with people who have perhaps seen a loved one or a family member die of breast or ovarian or prostate cancer, you can understand why they don’t want that to happen to them or other family members.

So, we spent a long time talking with families at risk who’d had different sorts of procedures or not. We talked with all the different sorts of healthcare professionals who are involved in this scene: the surgeons, the oncologists, the genetics counselors, the geneticists. And we were well aware of the fact that again, the sorts of things that people think will help patients and families make wise decisions are not always really spot on. So, we developed some materials, and we are running courses and programs for the healthcare professionals who may have to have conversations with families to try and enhance their skills. Because of all the interviews we did with families, we created our own family with some really tricky and interesting problems that weren’t exactly straightforward. And we included a deeply anxious, young woman who had been tested, but wasn’t at risk, but wanted to do anything to get both of her breasts removed.

And the program consists of lots of different videos with lots of exercises. And prior to doing the course, whoever it is, the genetics counselor, the surgeon, or the primary care physician, whoever it may be, they face the camera, have the patients that we will see in all our video vignettes asking them questions about their risk and what they should have done about it and who in the family should be tested. The participants do our course with all the different exercises, lots of group activities and then prior to leaving, they have these patients again on screen asking them the same questions, then independent coders rate the performance for knowledge and way in which the healthcare professionals impart information before and after the course. And when, and if we see that this makes a difference, like our previous educational programs have, we will then train facilitators all over the world to actually use the same materials.

Chris Riback: It is such a difficult area to think about and hear about because it also, to me, please can you correct me if I’m misinterpreting, it goes back to those questions of uncertainty and ambiguity that you were talking about before. I can’t imagine the tension and the stress that a person feels knowing that the BRCA gene [mutation] is in the family, knowing that something may have happened with a loved one and then trying to reconcile, within herself, the various choices and where they fall on that scale and having those conversations in a thoughtful, constructive way has to be central to helping a patient think through that uncertainty.

Lesley Fallowfield: Absolutely. And I think one of the things that’s probably more of a problem in the US than it is in other parts of Europe is the direct-to-consumer marketing of genetic testing. And I’m not certain what on earth a person does in such an uncontrolled way with the results that may come from that. So, we need to do a bit more, I think, in helping patients and families make informed decisions about what they ought to do. One of the things is that I always say this, and it’s true if you’ve got breast cancer, and if you’re at risk of breast cancer, breast cancer is an emotional emergency, it is not a medical emergency. And that means that you need to calm down, take a deep breath, take time to make a wise choice. It’s not a medical emergency, having something done next week is not as important as making a wise choice in a month’s time.

Chris Riback: The stress and pressure of time, it can overwhelm, and it can feel overwhelming. Dame Lesley, to close, I want to ask you about another quote of yours that I saw that had left me thinking and it’s not directly related to what we’ve been discussing, but a challenging personal area of thought as well. And that’s death. One quote of yours that seemed particularly profound to me, which of course is saying something, giving the other things that you say, was although grieving the loss of loved ones can be a difficult process, some people do speak about their loved one’s death as having been a positive experience. We need to demystify death and talk about it more. Now, most of us wouldn’t think of a loved one’s death as ever possibly being a positive experience. We are having this conversation about finding a cure, about extending high quality of life for as long as possible, but death is part of life. How is it ever possible for it to be a positive experience?

Lesley Fallowfield: It can be a positive experience if, in fact, one has gone beyond the dreams, the desire for a miracle to happen and for it not to be something that somebody is facing. When there is an acceptance that death is going to happen, that allows people to move on in positive ways and talk about real things that matter. I remember many, many years ago, when I first started working in this area, we still had a situation where doctors would not always be honest with patients or families about the fact that they were dying. And everybody got involved in this myth, this pretense that something else was going to happen. And it meant that people didn’t talk about real things. They didn’t laugh and cry together. And I was very struck about, when I used to do work in hospices, for example, that the families who actually faced the reality of death, sure they cried and looked upset with each other, but they laughed a lot. They still actually talked about realizable dreams and prospects. Whereas those who actually just were in complete denial about it, they knew they were dying really, but they didn’t have the same important conversations with each other.

So, in our grandmother’s days, death really was part of life, very few children lived beyond five years. Many died in infancy, infectious diseases killed lots of people. Death was more of a day-to-day thing and people talked about it. We’ve now got into a situation where no one talks about it and then the patient becomes almost a talisman for everyone else, as long as they can actually not talk about it, this person won’t die. And we have to talk about it more.

And we’ve been running lots of programs, until COVID of course came along, where we had a program run with the Wellcome foundation called the Departure Lounge, and we opened up in shopping centers and it looked just like a travel agency. And you went in and there were departure boards and luggage and everything. And it wasn’t obviously a travel agency. It was somewhere that people of all ages could come and just talk about death experiences. And we had some extraordinary experiences ourselves, actually looking at what families had always wanted to talk about but were denied.

Chris Riback: The difficult conversations, the conversations talk about uncertainty and maybe not ambiguity so much, it’s not so ambiguous, but it certainly leads to uncertainty. Dame Lesley, thank you. Thank you for your conversation. Thank you for the work that you have spent a career on for patients and doctors and the concept of quality of life. Thank you.

Lesley Fallowfield: Thank you, Chris. And thank you everybody who may listen to this for all your donations that allows all this wonderful research to go on. Not just mine and my team, but everybody else who’s funded by BCRF. Thank you so much.

Each October, BCRF-funded investigators are honored at the Foundation’s Symposium & Awards Luncheon in New York City. This year, the program was held virtually, without the lunch—but with all of the important conversations and ideas.

The annual event announces the Foundation’s grant investment for the coming year and recognizes BCRF investigators for their trailblazing scientific inquiry. It also provides a rare and unique opportunity for BCRF researchers to come together to share ideas and collaborate with fellow colleagues from around the world. About 215 of BCRF’s 275 researchers attended the live, online event.

This year’s program included an extraordinary symposium, moderated by BCRF Scientific Director Dr. Judy Garber, that included:

• Dr. Angela DeMichele from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center.
• Dr. William G. Kaelin, Jr. from the Dana-Farber Cancer Institute. Dr. Kaelin is the recipient of the 2019 Nobel Prize in Physiology or Medicine and was honored with BCRF’s 2020 Jill Rose Award for Scientific Excellence
• Dr. Lori J. Pierce from the University of Michigan. Dr. Pierce is a member of BCRF’s Scientific Advisory Board and the 2020 American Society of Clinical Oncology president.

We’re proud to make their discussion available in a special episode of Investigating Breast Cancer. You can also watch the recording on our YouTube page.

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Read the transcript below:                 

Chris Riback: This is a special bonus episode of Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation [featuring] conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship, and metastasis.

The panel was moderated by BCRF’s Scientific Director Dr. Judy Garber of Dana-Farber Cancer Institute.

We’ll have our regular episode of Investigating Breast Cancer in the next couple of weeks. Now, here is Dr. Judy Garber and BCRF’s 2020 Symposium.

Dr. Judy Garber: Hello, and welcome to the 2020 BCRF Symposium and what would ordinarily be the luncheon. I’m Judy Garber. I’m the scientific director of the Breast Cancer Research Foundation, and I’m a breast oncologist and cancer geneticist at the Dana-Farber Cancer Institute in Boston. It is our privilege today to have three investigators join us here to talk about breast cancer, progress in breast cancer, challenges in breast cancer, how are we living with COVID, and to bring us really to the frontlines of progress in this important field.

So Dr. Angela Demichele, from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, Dr. William Kaelin, who is the winner of the 2019 Nobel Prize in Medicine, from the Dana-Farber Cancer Institute in Boston, and Dr. Lori Pierce from the University of Michigan, who is this year’s president of the American Society of Clinical Oncology. So, Angie, would you like to tell us a little bit about yourself and your work?

Dr. Angela Demichele: Thank you so much, Judy. It’s really a pleasure to be with you all today. So I am a medical oncologist, I trained in clinical epidemiology and clinical trials. And so I do some clinical care and a lot of clinical research. I work both within my own group doing original research, but also within several different consortia. I co-chair the breast committee on one of our cooperative groups, the ECOG-ACRIN group, and I work in several other large groups.

Dr. Judy Garber: Thank you. Bill?

Dr. William Kaelin: So I’m also a medical oncologist by training, but in the ’90s, I pivoted towards laboratory-based research. I try to understand the functions of specific genes, particularly genes that are mutated or altered in various cancers. And I try to use that information to develop better therapeutics. And in that regard, I work with a number of both pharmaceutical companies and biotech companies to try to use laboratory-based knowledge to help create the next generation of cancer drugs.

Dr. Judy Garber: Thank you. Lori?

Dr. Lori Pierce: And I am a breast radiation oncologist, and I focus on clinical research and clinical medicine as well as translational research. And our research as of late has really been focused on those tumors that tend to be more difficult to control, following standard therapies, lumpectomy, and radiation. And so we’re really focused on how best to select those tumors and what strategies we can use to overcome radiation resistance.

Dr. Judy Garber: So you can see that everyone is extremely well qualified to answer our questions today, and to tell us all about what’s happening in breast cancer and what’s going to be happening in breast cancer. So, Bill, let’s start with you. The Nobel Prize, it is the prize. It’s a huge deal. And I think everyone is always excited to hear about the work that actually led to the prize for you. And a little bit of the impact of that work has had on cancer research.

Dr. William Kaelin: Yes, thank you, Judy. So I shared the prize with Gregg Semenza and Sir Peter Ratcliffe, for the work we did that allowed us really, for the first time, to understand how the cells and tissues in your body sense how much oxygen they’re getting. And if they’re not getting enough oxygen, to then respond appropriately, to survive in a, for example, low oxygen environment. This turns out to be very important for cancer because cancers are constantly facing a battle, trying to get enough oxygen to allow them to grow and to spread.

So now that we understand the molecular circuitry, if you will, that controls this response, we now have newer drugs being developed that, for example, can prevent the cancer cells from getting enough oxygen. And hopefully, stopping them in their tracks. But there are also some other new drugs that are helping patients make their own red blood cells based on this knowledge. And that might be useful for people who are developing anemia as a result of chemotherapy treatment.

Dr. Judy Garber: It’s so wonderful to hear you make it something that we can all understand. But it’s hugely important. No one doubts the importance of oxygen. Lori, so the breast cancer community, like our national community, has really begun to grapple with issues of racial and ethnic disparities, and justice in our own world. And you have made this a centerpiece of your ASCO presidency, which is quite a big pulpit. Can you talk about this issue for us and educate us on what we should know and what we should be thinking about from BCRF and beyond?

Dr. Lori Pierce: Sure, I’m happy to. So as you mentioned, I was honored to have been elected president of ASCO. And when you’re elected, as you probably know, you get to pick a theme. And so a year and a half ago, I picked the theme of equity of care because equity has always been so very important to me. As an African American, I’m acutely aware of the disparities for people of color. In almost any metric, no matter what you look at, people of color do less favorably. And certainly, cancer is no different. And so I knew I wanted to pick equity as my theme. And so my theme is equity; every patient, every day, everywhere.

And of course, since that time, equity, or I should say the lack of equity has been front and center for all of us in this country, in the world. And there has to be change now. So I think we all need to have a vision. I think we all need to have a plan for change. And so, what is my vision as being ASCO president? If you provide equitable care, you decrease the disparities that exist. And some of the disparities are due to social determinants of health, like where people live, their level of education, where they work, their financial resources. And it’s hard for us to directly impact those. But we can impact how we give care, and that is equitable.

And so much of what ASCO was doing already was focusing on so much of what BCRF does, is absolutely consistent with that. So some of the initiatives that we’re doing at ASCO, we are focusing on clinical trial participation, because we know that underrepresented minorities are underrepresented on clinical trials. And we have an initiative with the Association of Community Cancer Centers, ACCC, that’s also focused on equity and bringing minorities in clinical trials. We’re working on that together, and so that’s a very exciting initiative. We’re learning more about social determinants of health, and we’re doing that in a space to educate our fellows and our junior faculty, because they are the leaders of oncology tomorrow.

And we’re also focusing on bringing more providers of color, and bringing more students of color into oncology because we know that African American and Hispanic providers are truly underrepresented. And perhaps, patients of color would feel easier interacting with providers of color. And to that point, BCRF is working with us on that. The BCRF funding that goes to the trainees for Conquer Cancer, ASCO, will now be dedicated to disparities research. So all together, we are collectively working together to decrease disparities and improve our patient outcomes.

Dr. Judy Garber: That’s great, Lori. That is a huge undertaking and a task that’s certainly worthy of all of the attention that you’re giving it. Thank you. Angie, you have taken on a very difficult part of breast cancer care in the treatment of metastatic disease, which is so challenging, trying to prevent metastatic disease and then trying to manage metastatic disease. Do you want to talk to us a little bit about your thoughts about where we are and what you are finding most exciting at this time?

Dr. Angela Demichele: Yes. Well, Judy, we’ve made so much progress in the last 40 years in our therapies for newly diagnosed breast cancer. And that’s led to many women being cured of their disease. But as any woman who’s been diagnosed knows, there’s a lot of activity initially to take care of that cancer when it’s first diagnosed; surgery, chemotherapy, radiation. And you get to the end of that. And the hope is that you’re cancer-free. However, I think as a practicing medical oncologist, sitting with women who are at that stage of treatment, there were so many questions.

How do I know that the treatment worked? And how do I know if the cancer will come back? And I think what’s really exciting is that the laboratory scientists have really taught us a lot in the last, I would say five years about what it is that actually leads to a recurrence. So we now know that there are very specialized cells that can leave the breast, that are resistant to those initial therapies. These cells can travel in the bloodstream and ultimately, make their way to the bone marrow, where they can essentially go to sleep. And these sleeper cells can stay there for months or years, or even decades. But something then causes them to awaken and to travel to other parts of the body.

My research is part of a translational center of excellence, which means that I work in translating that work from the basic scientists in the laboratory who have figured out these mechanisms, to then try to bring that into the clinic. We can do that now with some new technologies that enable us to measure the fragments of tumor DNA in the bloodstream to let us know if there are still microscopic cells around. We can also look in the bone marrow to see if those cells, those sleeper cells are there. And working with my partner in this effort, Lewis Chodosh, we’ve identified several different drugs that can actually attack the sleeping cells.

Those cells aren’t dividing, and so they are very different than the typical breast cancer cells that are in the breast when you’re diagnosed. They need different drugs. And so the laboratory work that actually was funded by BCRF and Dr. Chodosh’s lab, to help us identify some of these new drugs, now is funding a clinical trial BCRF is supporting, where we’ll be screening women who have finished all of their treatment, are now a couple of years out from finishing that, who will have a sample of bone marrow taken to look for the sleeper cells. And then if those cells are there, we have the opportunity to give these women treatments. And these treatments vary from drugs that will attack the cells themselves, but also we’re looking at how we can help the immune system actually recognize that the cells are present.

Because ultimately, it’s a failure of the immune system to clear these cells. And so new immunotherapy approaches give us the opportunity to help the immune system recognize that these microscopic cells are there. And hopefully, clear them from the system before they ever can cause a recurrence or a metastasis. That ultimately, I think for many of us, feels like the last frontier in terms of how we can close that gap and ultimately, cure every woman who is diagnosed with the disease. And it also gives us an opportunity to develop tests that can help us to monitor a woman who’s had breast cancer.

So rather than simply wondering if this is going to come back, ultimately, we would love to have the ability to look for these cells, so that when you come into the doctor’s office, there’s a test that you can do that would help us know. Do you have any cells around that we could take care of? And that’s a much more proactive approach than what we currently have available. Much of this is still in the investigational phase, but I think it’s wonderful that BCRF has recognized how important this is, and is funding research in this area in many different laboratories and clinics around the country.

Dr. Judy Garber: Thank you. That certainly is exciting, and we are thrilled to be part of it with you. Lori, what’s going on in radiation oncology? And what’s new and you think will impact our high-risk patients?

Dr. Lori Pierce: When we generally treat patients following lumpectomy, we treat the whole breast with radiation. And then for those patients who would benefit from an additional boost, we give a boost to the tumor bed. But we’ve learned through the years that the outcomes are exceptionally well, particularly in some patients to the point that we may be treating too many patients. There may be a way to select those patients that perhaps, would do well. And be safely treated just with the surgery and systemic therapy, and not need radiation.

Because radiation, while it’s well-tolerated, there are side effects. And so if you can minimize the side effects by being clear for who needs to be treated and who doesn’t, then it’s great for all of us. So there are trials that are currently ongoing in the US and in other countries, including Australia as well, where patients with small tumors that are estrogen receptor-positive, that do not have lymph nodes that are involved, very favorable patients, particularly in postmenopausal patients, where we then use perhaps Oncotype, or other ways that we can discern those tumors that again, have a really, really good prognosis.

And we are omitting radiation. And we’re following them very carefully, to see that if with those selection criteria, we can arrive at a group of patients that will be successfully treated even in the absence of radiation. Just recently, there were two large trials, one from Florence and then a really large trial from the US, looking at patients getting whole breast radiation versus others just getting partial breast where just a portion of the breast is treated. And the recurrence rates at 10 years were less than 5%. So clearly, that is a group of patients that we know that are successfully treated with just treating a portion of the breast, and not the whole breast. And that leads to fewer side effects.

And then for those patients who do require whole breast treatment, we’re learning a lot about if we can shorten the treatment, giving more dose per day, but giving fewer days of treatment called hypofractionation. And we know from many scientific trials that you absolutely indeed can cut down the duration of treatment from the typical six weeks to four weeks. And now, with trials that just got released recently, there’s a trial from the UK showing you can give one treatment a week for five weeks, and have the same outcome as those who had the longer treatment. And that was 10-year data.

And then yet another trial from the UK showing that you actually can use five days, successive days, and treatments and have the same outcome as longer courses. And that, we have five-year data for. So there’s a lot of flexibility with how we can treat patients. And basically, we’ve got a toolbox now. We’re not treating everyone the same. We can help to identify those patients by their cancers that can have a range of options, and work with patients to figure out the best treatment for them.

With regard to high-risk patients, that actually gets it some of the research that we’ve been doing. And my partner in research is Dr. Corey Speers, an exceptional radiation oncologist, also here in Michigan, who has also been funded through BCRF. And we have looked at whether we can develop gene expression signatures such as what medical oncologists have been doing for so long, to help pick those tumors that are well-controlled with radiation. And those for whom, maybe more radiation or other options are necessary because they aren’t well-controlled with standard radiation. And so we’ve been looking at developing these signatures, and then also coming up with strategies for how best to intensify treatment.

For many years, I’ve been interested in this. And many years ago, I did a study with gemcitabine, chemotherapy, and radiation, because gemcitabine was known to be an agent that helped to sensitize the tissue. So you get more effect from the radiation to overcome the radiation of resistance that we see in a select group of tumors. And sure enough, the combined treatment was great with 100% tumor control, but the side effects were pretty significant. So even though the patients that were treated in the study said, “Oh, it’s okay, it’s okay because the tumor is gone away,” it wasn’t okay to me because I knew that there had to be ways to have more targeted therapies, that we could achieve excellent to control and not have the side effects.

And so subsequently, we have worked on PARP inhibitors and added radiation. Actually, an interesting story, and I’ll be very brief. I had just gone to a meeting at Oxford. I wanted to bring the PARP inhibitors into the radiation space for breast cancer. And so at that point, I said that we need to set up experiments, and I brought in Dr. Speers when I got back to Michigan. So we had to have experiments to show us how best to do this, and whether or not my hypothesis is correct that it really will sensitize tumors to radiation. And so thanks to BCRF, we were able to do these experiments. And sure enough, we found that sensitization, which we then carried to a phase one trial, which was also funded by BCRF. So we were able to show that indeed, PARP inhibitors and radiation, they were a very good combination. And now, thanks to all that preliminary work, there is now a national randomized trial, looking at adding PARP inhibitors to radiation. And none of that would have been possible without the BCRF.

And then finally, we are now looking at hormonal therapies with radiation, androgen receptor. We know that through preclinical information, data, that if you inhibit those androgen receptors with drugs that are readily available, and very well tolerated, that you overcome radiation resistance. And so we’re now looking at that. And that’s very important because androgen receptors are in all tumors, including triple-negatives. And so this may be a way of having yet another piece in armamentarium against triple-negative breast cancer. So there’s a lot going on right now in the radiation space. I’m so glad you asked.

Dr. Judy Garber:  So Bill, as the representative of the basic science community here, what are you finding the most exciting?

Dr. William Kaelin: Great question, Judy. So first of all, as you know, scientists are notorious for using their own private jargon. So I’m going to demystify a couple of things. The first is when a scientist talks about a gene, of course, a gene to a first approximation is a set of instructions for making a particular protein. So for example, gene A contains the instructions for making protein A, gene B contains the instructions for making the protein B, etc. Now, this is important because the question that our colleagues in the pharmaceutical industry and biotech industry are always asking, if we can make a new drug for breast cancer, should it be against protein A, should it be against protein B, et cetera? That’s really the job of the basic scientist, is to try to help them understand, what are the so-called targets they should be going after to develop their new drugs?

So I’m tremendously excited because as you know, for the past 20 years, we’ve had to first approximation, the identities or sequences of all the genes. But that of itself doesn’t help us very much. We have to understand the functions of those genes, and we have to understand which of those genes are altered in specific cancers. So an analogy I like to use is tumblers on a lock. You can think of any given tumor as a lock that had several tumblers, with each of those tumblers being an alteration in a different gene. And it was only when the right combination of genes were altered, that that cancer could evolve.

So now, as you know, with rapid advances in sequencing, for the first time, we can fairly quickly look at a particular tumor, find out exactly which genes had been altered, what were those tumblers, if you will, that led to that particular cancer, which really helps us inform a precision medicine approach of matching the right drug with the right tumor. Or put another way, with the right patient. Secondly, we have much more powerful tools now for identifying in the end of the day, which genes does a particular cancer care about the most for its survival? We sometimes refer to these as dependencies. And again, that’s incredibly valuable information for our colleagues in the pharmaceutical industry.

And so when thinking about it, I think it took literally decades to figure out that at least a subset of breast cancers cared deeply about the estrogen receptor, which of course, is the target of tamoxifen. With today’s technologies, you would have figured that out in less than a week. So I think that gives you some sense of how quickly things have changed. That’s partly because of a new technology called CRISPR that some of the members of our audience might have heard about, which allows us with really unimaginable precision, to go in and alter specific genes to begin to understand, first of all, what their normal functions might be. But secondly, to find out again, whether certain cancers depend on those genes. That’s revolutionizing our ability to identify potential new targets and various cancers, including breast cancer. And to try to take some of the guesswork out of drug discovery.

When I was starting out, a lot of drugs were discovered by sprinkling them on cancer cells and hoping some of the cancer cells died. That was a relatively blunt approach to developing new drugs. Now, we can really put forth to our colleagues in pharma, a list of experiments that gives them great confidence that were they to make a drug against this particular protein, it would have the desired outcome. Namely, to stop the growth of a particular type of cancer and potentially, breast cancer.

So I think we’ve come so far, to summarize in terms of our ability to know which genes are defective in different cancers, and to begin to understand the functions of those genes. And to understand which of those genes would be perhaps, most fertile for future drug discovery. So I think all of these things are incredibly exciting.

Dr. Judy Garber: I think where you share your enthusiasm about the fact that we can now, not only in the laboratory, parse out the genetics of the tumors, but the technology allows Angie to take her patients and figure out which genes in this patient are actually driving things. What should the targeted therapy target? And that can be done clinically.

So by the time it gets to a clinical place, it’s been perfected in the lab or adapted in the clinic, and on the tumors and in the cell-free DNA that’s circulating, so that we may not even have to get to the tumor. So here’s Lori’s got us thinking about ways we can cause less harm, or do things in easier ways. Right now, we have to look at the bone marrow. Someday, maybe we’ll be able to find those same cells circulating.

I think the Founders Fund was a place where BCRF said, and Larry said, we have to know about metastatic disease. We have to be able to sequence these tumors. And that’s what that money has been used for. So I think we all share your enthusiasm for that. And that as an example, with CRISPR, for the ways that technology lets us move forward. Angie, with research, where are our best opportunities? And what if we can’t follow them? What’s going to happen?

Dr. Angela Demichele: It’s been an incredible couple of years in breast cancer drug development, in particular. And for women who have metastatic disease, we actually have a wealth of new agents that really came about because of our understanding of the genetics of breast cancer, as Bill discussed. And so we have seen new drugs for HER2-positive breast cancer. We now have a drug called tucatinib that actually can cross the blood-brain barrier and help to treat women whose breast cancer has traveled to the brain. We’ve never had a drug in HER2-positive disease that could do that.

In triple-negative disease, we have the advent of immunotherapy. And we’re starting to finally see some great results in bringing checkpoint inhibitors that have been so successful in other cancers into breast cancer so that we can help the immune system recognize these tumors, and work with chemotherapy to eliminate them. And we have drugs in both HER2-positive and triple-negative disease that are these new antibody-drug conjugates. So we can take an antibody that actually docks to the cancer cell, link it to a chemotherapeutic so that that payload is essentially brought right into the cancer cell.

That’s led to the approval of a drug called Sacituzumab, for triple-negative disease, that has a high response rate. This is the most exciting drug we’ve seen in triple-negative disease for a very long time. We’ve also got that in HER2-positive disease. And actually, we’re now starting to see that maybe even tumors that aren’t covered in HER, aren’t those high HER2-positives. But even tumors that have even less of the HER2 could take advantage of this docking ability from these antibody-drug conjugates. So these are monumental changes that are giving months to years of life to women who have metastatic breast cancer.

And these targeted treatments have much less toxicity than chemotherapy that we used to give in the past. So that although we still have so much work to do for metastatic breast cancer, we are seeing now with these drugs, CDK4/6 inhibitors, others, that we can string these drugs together and give women with metastatic disease, a lot of time, and a lot of really good, quality time. And I fear that if we lose this momentum, we lose this pipeline from the laboratory to the clinic, to ultimately run the trials that are going to be able to show that these drugs can work, and get them out to patients. That we’re going to lose this wealth of knowledge that’s coming out of the lab, and we’re not going to be able to capitalize on that.

And we’re going to really stop this amazing progress that we’ve had with all of these new drugs over the last few years. And it takes time to do clinical trials. And it really takes a lot of infrastructure, which we have built over decades. And so we can’t lose that momentum and infrastructure, because we really will lose the whole next generation of treatments if we can’t keep that going.

Dr. Judy Garber: Lori, what are you excited about? And what are you worried about?

Dr. Lori Pierce: So I am excited about the advances that we’ve made this far, thanks to BCRF and others that have allowed us to treat our patients effectively, and decrease side effects. We know that with radiation, you can improve survival. And we know that with radiation if given the right way, our patients will have long-term tumor control. We know that we have to be very careful, obviously, in how our treatment is given. We must continue to have that forward momentum so that we continue to be even better at what we do. And that we can know when we can safely withhold treatment, and know when we do need to intensify treatment, how best to do it.

Dr. Judy Garber: Thank you. So let’s make a little shift here. We’ve talked a lot about treatment, we’ve talked a lot about trying to optimize treatment and not over treat, which is a great place to be able to think that we might be able to back off on some of these. But one of the wonderful things that lets us do that is that we have a lot of breast cancer survivors.

And of course, women who are surviving, they’re grateful, but many of them live with the long-term consequences of our treatment. And at least one of our audience is particularly interested in what we are doing to think about this challenge. So I wonder if, Angie, if I could start with you? Do you want to speak a little bit toward things that you are aware of, that have really become part of care, and what else we can be thinking about?

Dr. Angela Demichele: Yes, I think we have now recognized that women who are survivors have unique needs, that the experience of breast cancer and its treatment doesn’t end when the treatment ends. And so there’s been a really large effort now to focus on many of these long term side effects, particularly effects to the heart, that both our drugs and radiation can have. So there’s a lot of work now to try to understand whether there are markers in the blood, or even by echo that could tell us whether a heart is suffering effects later on so that we could start to intervene and prevent heart problems for women later on.

We have work going on for this issue of chemo brain that I know so many women really struggle with. And it’s something we don’t really understand very well, whether it’s an effect of the chemotherapy, or maybe in part, an effect of the hormone loss, the loss of estrogen that comes along with our therapies. There’s a lot being done right now to really try to understand this, as well as other side effects of estrogen withdrawal, which I think are the biggest effect on patients’ quality of life. The hot flashes, the joint pain, these are things that I hear day in and day out, that are just so bothersome, so difficult and get in the way of function. And so there’s a lot of research going on.

In fact, last year, we had a wonderful trial showing us that acupuncture could actually, in a randomized trial where half the women got acupuncture, and half of the women got what was called sham acupuncture, actually needles that didn’t really work, but really made the patients feel like they were getting it, it really showed that acupuncture made a difference in some of this long term pain. And so we’re really starting to think about not just drugs, but also alternative therapies that might be useful for these side effects.

And then as Lori touched on, I think the other really important thing is, we’re starting to realize that maybe the best way to take care of these long term effects is to prevent them from happening in the first place, by seeing where we can eliminate some of the most toxic drugs. So Adriamycin, the Red Devil, that drug really has a lot of long term side effects, including heart effects and bone marrow effects.

And now, with these targeted agents that we were talking about earlier, we’re seeing that those agents are so effective. That we may actually start to be able to take away some of the more toxic, less focus, less targeted agents, the chemotherapy, and still see excellent outcomes. And so we launched a trial this year, called Compass that is looking to eliminate Adriamycin from the initial regimen in women with HER2-positive disease. But we’re also looking at this in other subtypes of the disease.

And lastly, I will just say that the other thing that is still on the mind of many women, particularly with ER-positive breast cancer is this ongoing risk of recurrence, as we talked about. We’re starting to think about late recurrence, about what happens after five years of endocrine therapy, of the anti-estrogens. And planning trials that will actually utilize some of these new technologies to help us find women who might still be at risk five or 10 years down the line. And are there agents and drugs that we can use then to help prevent their risk? So things that we can do really many decades beyond the diagnosis that will help quality of life.

Dr. Lori Pierce: Can I add also, one thing?

Dr. Judy Garber: Please.

Dr. Lori Pierce: And that is that, and I applaud the member of our community who asked this question because I think it underscores how important patients are in the direction that research goes. If I had to think about how trials were written many years ago, and I don’t want to date myself, there was not a patient-reported outcome piece. And now, patient-reported outcomes are such an important part of our trials, so that we get that feedback. And we know the issues that really matter to patients. And that clearly, has colored our approach going forward.

Dr. Judy Garber: I wanted to make sure that we got a chance to speak directly to the ways in which COVID, which has changed our lives so much that we’re all here virtually, is affecting our patients and the way we’re thinking about the way we do patient care. And then, Bill, I’m going to ask you to speak about the way the COVID crisis has affected research. So let’s go in the other order this time. Lori, why don’t you start and talk about the ways you’ve seen COVID affect care of oncology patients?

Dr. Lori Pierce: COVID caused a significant change in how we would bring patients in. And we had to, of course, adopt physical distancing and the PPE. And we had to make sure we reassured patients that they were in a safe place, that they could continue to come for their treatments. With radiation, and I mentioned this earlier, we had been before COVID, even focusing then on abbreviated courses of treatment. So that was something that was particularly important to use during COVID. And actually, even beyond. And then we’ve adopted telemedicine far more robustly than what we had before. Radiation oncology, and I think part of the same thing for the other disciplines.

Fellow medicine was severely underutilized. We’ve had to work in this godawful pandemic. There should be something positive that we can take from it, and I think it’s telemedicine, that we can learn how to use telemedicine. Know when the appropriate times to use it, and be able to reach more patients that way than perhaps, we could before. We have to make sure that the playing field is level, that everyone has Wi-Fi, everyone has a way to access it. But with that, I think we will actually be even smarter in how we can deliver care, and certainly how we can do clinical research.

Dr. Judy Garber: Thank you. Angie?

Dr. Angela Demichele: I think it’s really important to recognize, we do things in teams. So we have clinical teams, and we have research teams. And when COVID hit, it really meant that overnight, we had to think about how to do things differently. We do understand now, that patients who’ve had cancer in the past are unlikely to be at increased risk. But it does seem that patients who are actively getting cancer therapy may be at increased risk, particularly if they’re getting very myelosuppressive or immunosuppressive chemotherapy. And so we had to make a lot of changes really quickly. And we worked as teams.

Initially, the operating rooms shut down because there was just too much risk of spreading COVID. So women who typically would have gone to surgery, all of a sudden, we needed to switch gears and start with chemotherapy. But we knew we could do that safely because we had trials that told us that it was okay to give the chemotherapy first, and then do the surgery. And so we were able to adapt by working as a real team on the clinical side, to find ways that we could do things safely for patients, minimize their risk, space out the time between doses, use boosters like the growth factors to make sure the blood counts didn’t get too low.

And really, help women get through this. Because clearly, breast cancer wasn’t going to stop just because COVID hit. And we really needed to make sure and continue to work really hard to make sure that COVID isn’t in any way negatively impacting how well we can take care of patients. We just don’t want any woman to have her therapy compromised, or her outcome really compromised by this pandemic, if we can help it.

Dr. Judy Garber: Thank you. And I think as you said, we don’t want women also to stop going for mammograms, or to stop being diagnosed early. If you feel something and you’re worried about it, don’t stay home and wait. There’s no reason. The hospitals and clinics are not unsafe places to go and get care. Waiting might be.

So I would use this time to say that when COVID is gone, breast cancer will still be here. And it’s our responsibility to make sure that we are still positioned to make progress against breast cancer. Our patients very much will still count on us to do that. But there’s not infinite money. There’s always going to be an issue.

Bill, what do you think is the most important and most concerning possible place where we really could be hurt, if we are unable to manage to do both, to deal with COVID and to still support breast cancer?

Dr. William Kaelin: I do worry about this next generation of researchers. They’re just getting started. They’re just starting their professional careers, but they’re also often just starting their families. And it’s like we’ve enlisted these wonderful people to join the battle, but I want to make sure they feel like we have their backs and that they’re properly equipped. So I just think it’s so important we remember the young people who we’ve had the good fortune to enlist in this battle against cancer and make sure they’re properly funded.

I couldn’t be more excited about the possibilities if we get this right. We now have this fourth modality, immunotherapy, to add to surgery, radiation, and medicine. And I think we’re in the early innings of what that’s going to be able to do for us. And I think we’re just beginning now, with these new tools, to be able to tell our pharmaceutical colleagues, the next generation of targets should be the following proteins. And if we inhibit these proteins, it’s going to dramatically change outcomes in this disease.

And the final thing I will say that, again, I’m preaching to the choir, we’ve known for decades that to cure a disease as complicated as breast cancer, we’re going to need effective combinations of drugs. Each of which is active in its own right. And each of which has hopefully a distinct mechanism of action. And you can just see it happening. We’re just about to get there. We have some wonderful agents that are now being used as single agents, or not quite yet in the right combination. You can see it. And so I can taste it. I can feel it. I just hope we get there.

Dr. Judy Garber: Thank you. Angie, I’m going to ask you to talk about something maybe you hadn’t planned to. But you talked about working in teams. And teams at Penn, but teams all over. Do you want to talk about collaboration a little bit, something, how you view this as an important factor?

Dr. Angela Demichele: Well, I do think that science has become so complicated. And everything we can do has tremendous potential, but no one person can really do all of the different things that are necessary to identify a target, develop a drug, bring it to patients, and ultimately test it and get it to market. So we have to work in teams because we all have complementary skillsets. And when we put them to work together, we can generate more than we could ever have done individually. And that’s the reality.

And I think that’s why many of us went into cancer research because we actually really enjoy these teams. And I know for myself, that is some of the richest time that I spend is really working with other investigators, whether they’re at my own center or across the country or around the world, really to talk about new ideas. I’m constantly learning. And then really, taking these ideas and trying to bring them to the clinic.

I just want to underscore what you said earlier, which is we figured out how to make the hospital and the clinic a safe place. And we figured out how to work in teams to give patients the best possible care, even with COVID. We really have to be sure that patients are coming, and they know that it’s safe. And they aren’t staying away because they’re afraid.

Dr. Judy Garber: Thank you for that. Lori, I’m going to let you close, and talk about something that you are in a place of leadership in cancer research, certainly in the COVID era. Cancer is not our only concern, but it is one of our concerns. And what I think we’ve heard so eloquently from everyone, are the possibilities that we just try not to let things shut down, we keep going. How would you like to close today, with all that you’ve heard and all the opportunities we have to make progress?

Dr. Lori Pierce: There’s been so much we’ve heard today, and the speakers have been so eloquent. As Angie said, the sum is bigger than the parts. So we all have our areas of expertise, and we bring them together in the best possible way on behalf of our patients. And we need to have continued funding, we need to continue to have that positive momentum. Yes, we all know that COVID was a major bump, but we are recovering. And we are moving forward. And we want to continue that momentum.

We don’t want to lose the next generation of researchers, both laboratory researchers, and clinical researchers, and clinicians. We need to continue to have the funding so we continue the forward movement. So we can continue to do the very best we can for our patients. And so I thank BCRF for all the funding you’ve provided. I thank you, BCRF, for the funding you will provide. We will beat this virus and we will beat this disease.

Dr. Judy Garber: Thank you. I’m sure that everyone would agree that we have more than 200 amazing investigators in BCRF. But we could hardly have done better than the three we’ve had with us today, trying to teach us all about breast cancer, to help us understand where are we going, where do we need to go to make us see that we have tremendous opportunities to continue to move forward.

Our patients expect and demand that we will do that for them, and we all want to. We are always grateful for the opportunities to learn from each other and work together. We thank BCRF for that as well. So thanks for being with us today, and thanks for a wonderful set session today. Thanks to you all.

Outro: That was BCRF’s 2020 Symposium and a special Investigating Breast Cancer podcast. Thanks for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.

Research shows that when chemotherapy is delayed, a patient’s chance of survival falls significantly. Dr. Mariana Chavez MacGregor joined our podcast to talk about her work with underserved and underinsured patients—those who are most likely to experience delays—to develop personalized ways to improve healthcare access and, ultimately, outcomes.

A JAMA Oncology study suggests that patients with a time to chemotherapy after surgery of 91 or more days had a 27 percent increased risk of death from breast cancer. Those who are at risk of these delays are often Hispanic and Black, Medicare and Medicaid beneficiaries, patients with more comorbidities, and those of low socioeconomic status. 

Dr. Mac Gregor is an associate professor at the University of Texas MD Anderson Cancer Center, holding a primary appointment in the Health Services Research Department and a joint appointment in the Breast Medical Oncology Department.

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Read the transcript below:

Chris Riback: Dr. Chavez Mac Gregor. Thank you so much for joining me. I appreciate your time.

Dr. Mariana Chavez Mac Gregor: Happy to join you and all your audience.

Chris Riback: Could we start with both what I assume is the simple and just frustratingly complex question that keeps you up at night and defines such a significant portion of your career. Why is breast cancer treatment sometimes delayed?

Dr. Mariana Chavez Mac Gregor: Well, that’s, as you said, a question that motivates me and that does keep me up at a night sometimes. I think that as a breast medical oncologist, I have seen firsthand how sometimes patients delay the initiation of their treatment. I have particularly focused on studying delays to initiation of adjuvant chemotherapy, which is the chemotherapy that starts after surgery. Meaning, patients who are already part of the healthcare system, they have a cancer diagnosis, they undergo oncological surgery, and then they delay the initiation of their chemotherapy. What my group and I noticed first, is that those delays matter, meaning a patient delaying the initiation of chemotherapy, particularly for triple-negative or HER2+ tumors, have worse outcomes than a patient that starts treatment, let’s say, within a month or two from surgery.

Dr. Mariana Chavez Mac Gregor: So, knowing that delays are detrimental for patient’s outcomes, then the question becomes: why are patients delaying treatment or who are the patients more likely to delay treatment? So that was a next step in our line of research and we identify patients using different, large national databases that represent what’s happening. We’ve seen over and over again that racial and ethnic minorities are more likely to delay their treatments, women at extremes of age, either those that are very young or very old, are more likely to delay treatment. Patients with more comorbidities, patients with low social economical status, low education levels are at higher risk at delaying their treatments, telling us that there’s some social determinants of health that are very likely associated with those delays. Not surprisingly, we saw that patients that are uninsured are more likely to delay the initiation of treatment.

Dr. Mariana Chavez Mac Gregor: Then we wanted to go even deeper because identifying which populations are at higher risk of delays doesn’t tell us the complete story. It’s not giving us the why and what I have been doing with the help of the Conquer Cancer Foundation and BCRF is working on the why and with a team of collaborators, we’re actually doing qualitative research. The difference in this type of research is that we are going to the story of the individual patient. We’re identifying patients that have gone through treatment delays and hearing their stories and trying to identify patterns in their stories to help us understand things at the individual level, but then extrapolating to really what is happening that can help us explain this delay, so then, of course, we can plan solutions.

Chris Riback: Yes, and I want to ask you about those patterns because that’s where a society wide set of solutions, I would assume, could be put into place. But as I was reading about this, particularly at this time of COVID, we all are getting a real time, even deeper education around many, many of the inequities around access to health care, around issues of comorbidity. So many of the things that you just described and we’re hearing about that.

By the way, I want to ask you as well, I’m sure that COVID is making everything even more complicated in your world and we’ll talk about that too, but just to hone in on one point that you made, these are women, these are patients who have had the surgery and you’re not talking about the sets of patients who have put off care and we all do it, who have delayed for whatever reason. But these are patients who have already had the surgery and now this is the next step, the chemotherapy. Was that even more surprising or frustrating to you because these are the women who are kind of right at that stage where they’ve gone through this particular challenge, now have the opportunity to start, we hope, making improvements, and yet there are barriers to their care.

Dr. Mariana Chavez Mac Gregor: Yes. I think there are, of course, many different ways to study treatment delays. There are many different time intervals that we can study. This was one that we thought was feasible and consistent, but with our findings, you can only wonder what would be the impact of patients delaying even a diagnosis because of fear or lack of access to health. So you can only wonder and imagine that the implications in terms of their outcomes are going to be even worse. Of course, I work at a large academic institution as a woman and as a breast cancer doctor, I am encouraged by the new drugs that we have access to and how we’re improving treatment for breast cancer patients. But from a very simple perspective, I think we should also think about how the great treatments that we already have can be delivered to the entire population on time, because maybe we’re missing a great opportunity to impact the lives of many, many cancer patients.

Chris Riback: So where does that begin? Where does that conversation begin? Maybe this gets to what you were talking about a moment ago, trying to decipher the patterns by talking to the individuals. What patterns are you seeing?

Dr. Mariana Chavez Mac Gregor: Right now we are in the phase of analyzing some of these interviews. As you can imagine, when a participant and a patient share their stories, there is a lot of material to go through. But part of that analysis has been really interesting. What we are seeing and some of those survivors that are hearing might identify with this, but we are identifying a pattern of shock, of either it is overwhelming information that can paralyze some women into that next step, right? They’re hearing that they have to go through chemotherapy and suddenly it’s like their life, it’s in shock. There are fears, there’s a stigma about cancer. There is worry that it’s, of course, valid regarding the finances, regarding job security, regarding the responsibilities that specific patient’s living at the time. Of course, those are very different for a patient with little kids compared to another one that is young and wants to have kids and wants to think about preserving for fertility. Or to older women that are the primary caretaker of a family member.

So that role in that moment gets, of course, shaken by the news of chemotherapy. We’re seeing that in some patients it takes a while to get them to the action, to get ready to do it. We are seeing through different layers of analysis, in one way or the other, how crucial and fundamental support is. Support can come from other breast cancer survivors, from family, from friends, from community, from a place of worship or members for those that practice a specific type of faith. But that support from others becomes very, very relevant. Something that has been very interesting, and in that regard I think maybe we as providers are the ones that can solve this. We have found very little insight in terms of the delay, meaning all of the participants that we’re interviewing experience initiation of chemotherapy delay. All of them. It was part of the criteria to invite them to be part of this study.

The majority of them think about them as having experienced a delay in the initiation of their treatment. I think that might then fall into us as providers. Maybe we don’t talk about the importance of timely treatment enough. So, I think that is very interesting and that tells us about the shared responsibility that we have of interest. We, of course, have seen some or have heard some stories related to travel to the hospital to receive treatment or to insurance. But again, let’s remember that these participants that we’re interviewing, all of them, are already emerged.

Chris Riback: They’re in the system.

Dr. Mariana Chavez Mac Gregor: Correct. These are not patients that are thinking about, “Should I get a mammogram?” Or, “Oh my God, what do I do? I have a lump. I don’t have a doctor.” Right? We are talking to women that already knew they had cancer, that underwent breast cancer surgery, that had a team of doctors. Some of them want a second opinion, et cetera, but it is a highly selected group of women if you think about that way.

Chris Riback: Yes. What also sounds to me in listening to you that would just make it such a complex problem for someone like you or other providers to unwind is, is this a social problem? Is this a societal problem? Is this a public policy problem? Is this a health problem? Is this a psychological problem? Is this a cultural challenge? I mean, where do you begin in thinking about how to get to the heart of the why?

Dr. Mariana Chavez Mac Gregor: I honestly think this is multi-dimensional. All the factors that you’ve mentioned, I am convinced they play a role and they might play a more or less significant role for each individual patient. But, of course, I think there are common themes. Social inequality, we know that affects healthcare outcomes. That is not new. We see it over and over again in breast cancer and other diseases, and we can talk about this, but of course, we’re seeing that with the COVID pandemic. So social inequalities matter. Language matters. Navigating the healthcare system, it’s quite complex. You almost need even more than a PhD to understand an insurance bill. It’s very complicated, can be overwhelming. I think, of course, policy matters. There’s a project that relates to this, that I am doing. We just submitted this data to the San Antonio Breast Cancer Symposium and are starting to work on the manuscript.

But what we are doing is we’re looking at a very large national database and we’re evaluating the time to treatment, time to initiation of chemotherapy, the same group of patients, right, to be consistent. Finished surgery, looking at the initiation of their treatment and then looking at the differences between whites and Hispanics, and whites and African Americans among women diagnosed with breast cancer in states that underwent Medicaid expansion in 2014. So this is a policy because you were asking about policy. So, the question is can we, with policy, decrease the time to chemotherapy initiation, one, and two, can we, knowing which are the populations that are more effected, maybe with this policy decrease this gap? Our analysis so far, what it’s showing us is in this group of states, if we compare free Medicaid expansion and after Medicaid expansion, there was a decrease in the time to chemotherapy initiation.

Dr. Mariana Chavez Mac Gregor: So, the proportion of patients that delayed treatment decreased, and we saw delay regardless of race and ethnicity. So we saw benefits across all the subgroups that we studied. It’s a little complicated analysis, we call that a difference in difference analysis. But what we saw is that big gap between whites and African Americans and whites and Hispanics shrank in those patients after the Medicaid expansion, suggesting that these policies that have a set goal decreasing disparities and increasing access to care are really giving the results that are meant to have. That tells me that this shared responsibility that I was talking about, of course, physicians and providers and medical oncologists like me are responsible to discuss this with our patients to inform them about the importance of timely treatment initiation. But that as a society and as policymakers, there’s also a responsibility to facilitate that access to care.

So I think it’s psychological. I think it’s medical. I think it’s policy. It’s quite complex and many of the members of your audience, I’m sure they can identify about this almost snowball of things that a woman has to go through just to get there. I’m sure that some cases can be smooth, in some cases it’s a longer journey, but I think we do have a shared responsibility and only implementing strategy that touch on all these dimensions. We are going to be able to expedite treatment initiation, because if we think about strategies and some of this we’re going to try to pilot in a small study with patient navigators, for example. Well, there’s so much that a patient navigator can do if they don’t have the buy in from the providers, or there’s so much a patient navigator can do if a participant does not have access to healthcare. So, I think it has to be multi-dimensional.

Chris Riback: What is a patient navigator?

Dr. Mariana Chavez Mac Gregor: So patient navigators can be nurses or a social worker.

Chris Riback: I see, so people who help a patient through the process.

Dr. Mariana Chavez Mac Gregor: Correct, and that literally help you navigate that enormous sea of things. Right?

Chris Riback: Understood.

Dr. Mariana Chavez Mac Gregor: Understand scheduling, makes sure that things don’t fall through, that if you need help with transportation, for example.

Chris Riback: Yes. That’s major. I know.

Dr. Mariana Chavez Mac Gregor: Language. I mean, it may sound minor, but if you need public transportation or your finances are not allowing you to pay parking for every week the hours that you’re going to spend at the hospital, you’re more likely to not go. Access to support groups. So those are some of the things that a patient navigator can do, almost like walking you through the journey. As I was saying, I think patients are going to have different needs. Some might have needs with language. Some might have needs with travel. Some might have needs with facilitating visits with all their providers, because if they have a lot of comorbidities, sometimes we as doctors need them to get those other comorbidities under control before we start treatment. Right?

So there’s also the medical part of it. There might be times that I cannot start treatment because there’s an open wound because the surgery didn’t heal, and it may not have healed because that patient has poorly controlled diabetes because she’s not able to have regular follow-ups. So, it can be very, very complex, and I’m afraid that solutions are going to have to be, as I said, multi-dimensional. Because if they’re too superficial, we might not see the change that I think we all want to see.

Chris Riback: Yes. It sounds extremely complicated. The sliver of hope and I’m a hopeful person by nature. In listening to you and thinking about the times that we are in. I mean, when you talk about ideas like shared responsibility and the importance of public health and the role that public policy can play in challenges like the ones that you’re describing, we are living through a moment, with COVID in particular, where I think many, if not most of us, are understanding the role that public health can play and a coordinated policy can play and must play in terms of keeping people safe, healthy, and going about their lives. So in thinking about that and thinking about the COVID situation, first of all, you may or may not agree with the statement I just made. So if you think that I’ve got that wrong, please let me know. Then secondly, how has the COVID situation complicated all of the complications that you’re already describing?

Dr. Mariana Chavez Mac Gregor: I do believe that we all are living in unique, challenging times. The COVID pandemic, it’s clearly affecting the entire world and some people have been greatly affected in terms of health and job security, et cetera. Something that has been very interesting from the perspective of the disparities research that I’m interested in is a lot of people are noting while we all can are vulnerable to COVID, some groups are dying more from it. This is something that it’s been seen not only in the United States but across the world. We know that more African Americans and Hispanic minorities are dying of COVID. We know that the elderly, we know that cancer patients, but there is a social distribution if you want to call it that. This has been a lot of interest for a lot of people, including the news media.

Dr. Mariana Chavez Mac Gregor: What I think it’s very important to mention is that while this is tragic, this is not new. This same phenomenon that we’re seeing with COVID, we have been seeing for a while in breast cancer, in other cancer, in chronic diseases. So, there is a disparity in outcomes. A lot of researchers from BCRF, many of them also supported by the Conquer Cancer Foundation, have described and tried to understand the disparities that are very clear for breast cancer. So we are just seeing in greater magnitude, or maybe closer to us, what happens in many other conditions. Now, the current COVID crisis, it’s posing many challenges for patients and, of course, for the healthcare system. Talking specifically about cancer patients, we are seeing a lot of cancer patients that aren’t getting their treatment. If not interrupted, at least delayed. In this case, it’s not because patients are doing anything wrong or we’re doing anything wrong. It’s just the circumstances.

Dr. Mariana Chavez Mac Gregor: In Texas, for a while, there was a government mandate to decrease certain types of surgeries because the hospitals were at capacity because we needed to have PPE for medical personnel, a number of reasons. These are public measures aimed at protecting the overall population, but that at the individual level may have costs or are costing for some patients not to receive the expedited treatment that they would have otherwise received. Similarly, we think about our screening programs. Every year and every month, actually, thousands of women participate in screening programs and they are diagnosed with early-stage breast cancers. Well, what if now, giving the situation, we are not able to get our mammograms sometimes? I can tell you, I personally was due to have my mammogram in June. It’s July. Maybe it’s just a month. I don’t think it’s such a serious problem, but it’s becoming harder to access the healthcare system because the healthcare system is saturated and carrying a very sick patient. Similarly, individuals that have lost health insurance, giving loss of jobs, so they’re not able to look for help.

Dr. Mariana Chavez Mac Gregor: So, I do think, while I have not studied it or measured it, I think we are going to see some of these unintended consequences from the COVID pandemic in breast cancer and in other cancers and medical problems. Unfortunately, that is my fear. Now, trying to be, I think, optimistic, as you said, there are of course a lot of organizations like BCRF, many healthcare institutions that are trying to work extra hours, to open our doors, to make sure that we’re available to provide patients the care they need and their reassurance that even in the circumstances, we’re going to give them the best possible care.

Chris Riback: Yes. So much. Now what you just described would be the last thing that anyone needs: More obstacles and challenges in what’s already, as you’ve described, a really challenging and complex situation. So, it is fascinating to listen to you and hear you talk about the ways that you seek to help others. Can we talk for a moment about you? As far as I can tell, you’ve studied in Mexico, the Netherlands, St. Louis and then Texas, which to be fair, by many people’s count, that actually would be a country on its own. So let’s call it four different countries. How many languages do you speak?

Dr. Mariana Chavez Mac Gregor: No, not that many. Not that many. I was born and raised in Mexico. My family’s there. That’s where I did medical school. I always wanted to be a cancer doctor and I became convinced that I wanted to be a breast cancer doctor when I was in medical school, and I was probably around 21 or 22 years old. So that became my dream. I went then to the Netherlands to do a Master’s in Clinical Epidemiology, and I worked with a wonderful group evaluating breast cancer risk factors as a way to prepare myself and to position myself better to get the best possible training here in the United States. That’s how I got fortunate to be accepted to the Internal Medicine Residency Program at Washington University in St. Louis, and then medical oncology training at MD Anderson. I’ve been faculty here for now almost nine years, and the tenure associate professor. I love what I do. I’m committed to my patients and I do love to travel and learn from different cultures and places. That is something that keeps me moving.

Chris Riback: Yes, I’m sure that it does. In thinking about it, that can’t be a mistake. The area, the particular area and the particular issues that we’ve been talking about within breast cancer and treatment that you have taken on personally, I can’t imagine that that is separated from your own personal history, your own growth, the places that you’ve lived, the people that you’ve met, the cultures that you’ve studied. Is that right? I mean, is this a natural progression for somebody of your spirit who would have spent so much time in so many different locations?

Dr. Mariana Chavez Mac Gregor: I think it is. Of course, I have a total bias with trying to understand distribution of health and disease in different populations. As I said, I’m from Mexico, I’m committed to the health of Hispanics. It is who I am. It is where I’m coming from. Of course, it’s a very important area of research where I can see that we can make a difference and that has really filled me with passion and with a sense of purpose. But I think you’re right. It’s closely linked to who I am, to where I grew up, or the things that I’ve seen. I have been fortunate to care for a very large number of patients and I’ve seen extremes of very privileged patients and patients in very difficult circumstances, and I have to help them all.

For me, it’s how can we as a society, as a healthcare system make sure that all patients get the best possible care? Because that’s what we all want, to be able to get the best treatment for all breast cancer patients, to give them the best possible outcomes, regardless of who they are, where they’re from, what language they speak. I think that’s the ultimate goal that we all have, and that BCRF has had supported. I am incredibly thankful for all their support. A lot of this I couldn’t have done without the support of them. That, of course, comes from so many of the patients and survivors and family members and audience that you reach. So thank you so, so much.

Chris Riback: Thank you. What you just described about your goals and what you want to do certainly comes across so strongly in getting to talk with you. Dr. Chavez, Mac Gregor. Thank you. Thank you for your time. Thank you for the work that you do.

Dr. Mariana Chavez Mac Gregor: Thank you. It’s been my privilege.

For young women, a breast cancer diagnosis presents a unique set of challenges not only due to age but the biology of the disease as well. While a diagnosis under the age of 40 is rare, the disease tends to behave more aggressively. Compared to older breast cancer patients, young women treated for the disease tend to have an increased risk of experiencing emotional distress, treatment-induced sexual dysfunction, and concerns about future pregnancies.

This is where Dr. Ann Partridge steps in. Her BCRF-supported research seeks to understand the complex issues young women with breast cancer face. Dr. Partridge studies the biology behind their breast cancers as well as focusing on how young women make their way through their experiences – whether it’s physical or emotional.

A BCRF researcher since 2016, Dr. Partridge is co-founder and director of the Young and Strong Program for Young Women with Breast Cancer and serves as the Director of the Adult Survivorship Program at Dana-Farber Cancer Institute and Brigham and Women’s Hospital. Dr. Partridge is a Professor of Medicine, Harvard Medical School.

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Read the transcript below:

Chris: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis… which just happens to be the topic of today’s conversation.

A breast cancer diagnosis for anyone, of course, can be life-altering. For young women, it can be even more difficult: Not only because of the time in life – finishing school, building careers, raising families – but also the biology: The cancer can be aggressive, and the chances for recurrence significant.

Which is only part of what makes Dr. Ann Partridge’s work so important and remarkable. On the biology, among the areas she studies is the “why”: Why is the cancer so aggressive? But she also focuses on the how: How these young women will make their way through the challenges.

Dr. Partridge is co-founder and director of the Young and Strong Program for Young Women with Breast Cancer, an extraordinary, unique offering that has guided more than 4,500 young women on their journeys through and beyond cancer, offering comprehensive care, support, and education tailored specifically for them.

More on Dr. Partridge: She is a Professor of Medicine at Harvard Medical School and serves as the Director of the Adult Survivorship Program at Dana-Farber Cancer Institute and Brigham and Women’s Hospital. She has been a BCRF Investigator since 2016.

Chris Riback: Dr. Partridge, thanks for joining me. I appreciate your time.

Dr. Ann Partridge: My pleasure, Chris.

Chris Riback:  Breast cancer, of course, presents an incredible challenge and fear for any patient. Let’s focus on what you focus on – What is different, maybe harder but definitely different, about breast cancer in younger women? And for purposes of the conversation, and I guess for purposes of your work, how should we define young?

Dr. Ann Partridge: That’s a fantastic question to start off. And I completely agree with the first premise, which is a cancer diagnosis and breast cancer specifically is a scary diagnosis. It’s scary for women or men of all ages, but it is probably the most scary for our youngest patients. And that’s with good reason. And when we think about young, we’ve seen in numerous data sets over the years, many studies, many populations both in the United States and across the world, that when a young woman develops breast cancer, on average she’s more likely to die of it. I mean, that’s just the stark reality, even in 2019, and that’s not okay. That’s not acceptable, right? We need to improve cancer care and breast cancer care specifically, which of course is the mission of the BCRF, for women of all ages and particularly for our most vulnerable, those who are at higher risk of hearing from it again and potentially succumbing to it.

So that’s the reality for young women, and that’s why they’d be more scared. And young here can be defined at 40 or younger, which is where the data are most robust, the strongest data to support that there’s a higher risk of hearing from breast cancer again, and having to fight it again, and potentially dying from it. So that’s the stark reality of the age disparity.

And the things that are different for young women, beyond a higher risk of recurrence on average … It’s not true that every young woman’s high risk, but on average are that, one, young women are more likely to get the more aggressive breast cancers. So when we think about the buckets of breast cancer, young women are more likely to get the higher grade, HER2-positive or triple negative breast cancers. The incidents, the likelihood of those occurring as women get older go down, and so they’re more common in younger women. That’s one. Two is young women typically aren’t screened. In this country, we don’t begin mammogram screening, which is our gold standard screening, and it’s the best we’ve got for populations. It’s not perfect, but we don’t even begin doing that until women are in their thirties or forties. And so in young women, you’re typically getting an unscreened cancer diagnosis, which means the tumors are bigger, and they’re more likely to be node-positive. And part of that also has to do with the biology of the tumors they get, those higher risk tumors.

So you’ve got this double whammy of being more likely to get more aggressive disease, and more likely to have it be more advanced when it’s detected for the youngest patients. That’s kind of the biology stuff. That’s the disease stuff. And then you add on to that, and this is where young women are really different because older women can get risky tumors, and they can obviously be diagnosed with more advanced disease. But young women are diagnosed at a time in their lives when no one expects breast cancer. But women going in for mammography are getting screened for a cancer, right? So they know that they’re at risk for it. Young women are just busy, living their lives, trying to start young families, trying to start careers, trying to get through school. And then, wham, they can be hit with a breast cancer. And it’s completely unexpected and completely non-normative. It’s not something that their friends are facing. And then of course all the treatments and all the side effects. Even if you don’t need that much treatment, a young woman having hot flashes at the age of 30 compared to her peers who are out, again, having young families, partying, whatever they’re doing, making romance. This is not something that you have peers to support you for or that you remotely expected.

And so this is another area where there is a disparate problem for young women. They’re more likely to suffer, even if they’re going to survive. And the vast majority will survive their breast cancer, thank goodness. Even though it’s worse for young women, they still are most likely to survive and do well in the long run from a disease standpoint. They’re more likely to suffer emotionally and socially because of the diagnosis of breast cancer. Those hits occur with beauty, sexual health, fertility, emotional health, anxiety, fears, depression. These are all the things that young women are more likely to have to contend with. So, all of those things come together and just make it just harder for young women to be diagnosed, treated, and then kind of thrive beyond the breast cancer.

Chris Riback: It’s quite an overwhelming set of factors. And a couple of things jump out to me. One is, and this seems exactly consistent with what I take from your approach to this challenge. It’s an incredible combination of the biology plus the emotional. As we both stated at the top, that’s surely the case for everyone who suffers from this disease or any disease. When any of us gets something unexpected and something so potentially dire, that’s very shocking to say the least, and there’s that combination of biology plus emotion. But you’re describing the unique components of it for this segment of the population, and so I want to talk to you about that.

A couple of questions to make sure I’m understanding on the biology portion so that we can level set there. What’s the why behind it being, on average, a more aggressive form of breast cancer? So I’m getting the fact that young women won’t have mammographies necessarily in practice. And so I get the fact that because of that, when they’re noticing breast cancer, when that’s coming up, it might then be at a later stage, in a more advanced age, et cetera, et cetera. But why a more aggressive form? Why does that go more towards this audience than not?

Dr. Ann Partridge: That’s the million-dollar question. And to be honest, we’re not 100% sure. That’s what a lot of our researchers are working on, including myself. That being said, some things we do know that point in the direction of why. One is that young women are more likely to have a hereditary predisposition to their breast cancer. They’re more likely to have a BRCA1 or two mutation, or some of the newer genes that we now know predict breast cancer risk and the development of a cancer. And those genes are associated with developing more aggressive breast cancers. So, for example, BRCA1 mutation carriers, it’s more prevalent. The hallmark of having a mutation is early onset breast cancer or young age. They’re more likely to have triple-negative breast cancer, which is one of our more aggressive subtypes. Young women or people with p53 mutations, which is fortunately rare, are more likely to have HER2-positive breast cancer, which is more aggressive. The good news is we have really good and effective treatment for it these days, but they’re more likely. Those tumors tend to be larger, node-positive, and require kind of a kitchen sink approach, on average, for the treatment.

So, some of it’s the genetics. And then you know the rest, we’re trying to work that out. And there’s some really interesting kind of early data suggesting that there may be some kind of deeper genomic changes in the tumors that arise in young women, and that there may actually be some evidence that women who are immediately postpartum, meaning having recently had a baby, that the biology of the cells as the breast changes back to a not postpartum state may increase the likelihood in that short term of a more aggressive biology of cancer. There’s some data suggesting that, certainly not ready for prime time to think about with patients yet, but we’re to figure that out.

Chris Riback: Two questions then: One, one the genetic factor and that component. Is it proper of me to believe that women who have a genetic predisposition, whose mothers, older sibling, older sisters, aunts, et cetera, grandmothers, that that they would be more likely to potentially get mammograms at an earlier age. And so therefore when you talk about, which I would assume to be the case, that many women don’t get them at an early age. We don’t give them until 30. Are you talking about a subset who don’t have a genetic predisposition, or is it even the case that with a genetic predisposition too many women may be in a situation where they’re not getting mammographies at an early enough point? That was one question. I’ll ask the other one-

Dr. Ann Partridge: Yes. There are too many women who have family histories who aren’t having this discussed, who aren’t getting tested, and who aren’t getting any screenings, even when they have a hereditary predisposition. And you could be tested and be found positive. In the general  population, just to clarify, the current guidelines for screening range, depending on which group you’re looking at, whether it’s the US Preventative Services Task Force or the American Cancer Society, range from starting at 45 to starting at 50. So your average person in the population, a proportion of whom will have an unknown hereditary predisposition to breast cancer, they’re not even being recommended to get screening until they’re beyond the young age of breast cancer. That’s one.

Two is, even when we know someone has a hereditary predisposition, and we do start screening, the recommendation is 10 years before the earliest onset of breast cancer. So if a woman with a BRCA1 mutation had a mother who had breast cancer or a father’s sister who had breast cancer in her thirties. Let’s say we start screening at 25, and we do mammograms alternating with MRIs, which is what we recommend, generally, if she tests positive. Even in that setting, A, our imaging isn’t perfect. Mammograms are not great in younger women because its breast tissue is more dense. MRIs are more sensitive, but they’re still not perfect. And then the other thing to remember is that screening is not prevention. And so screening might pick it up earlier, yes, but it’s still going to be a cancer.

Chris Riback:  You’re seeing it there. That is such a, such an important point.

Dr. Ann Partridge: And so that’s where we offer women prevention, which is a heavy load too, if they’re very high risk. But that’s a really hard thing also to offer a young woman when she’s, again, in this kind of developmental life stage where the idea of taking breasts off or taking out ovaries when you haven’t had your babies yet, especially, for many of these young women. Especially in our society, many women are waiting for lots of good reasons. That’s a pretty challenging situation as well.

Chris Riback: Yes. That is not part of the narrative, or the expected narrative, or the desired narrative for anybody, no doubt, particularly at that age.

Dr. Ann Partridge: And the good news is we have lots of supports for these patients. For these women who we call “previvers,” who are at risk, we’ve got lots of work going on to try and support them to make the best decisions for themselves, whether it be prevention or monitoring, and aim for early detection, if they’re ultimately going to get a cancer. And then, of course, once women develop the disease, if they’re destined to, to get them through and beyond. So I don’t want to be all gloom and doom here. It’s just it’s a tougher fight, and you need more to support our younger patients.

Chris Riback: And I want to ask you about some of those efforts, of course, particularly your programs. “The Young and Strong Program for Young Women with Breast Cancer,” which by the way, that’s just great branding, young and strong.

Dr. Ann Partridge: Thank you. Came up with by one of my patients, by the way. One of my patients came up with that.

Chris Riback: I hear that. So you do get so many scientists, researchers, doctors, caregivers do get great feedback and insights from their patients. I have heard that. So, that’s terrific. And I’m sure you share all of the royalties off of merchandise and all the selling of stuff.

Dr. Ann Partridge: Yes, if only.

Chris Riback: Yes, I know.

Dr. Ann Partridge: That part, we need some help with.

Chris Riback:  I understand. And I’m teasing, of course.

Dr. Ann Partridge: Thank you BCRF, given our lack of ability to get our own royalties in this world… at least in the clinical side.

Chris Riback: That’s not what we’re looking to you for. We’re looking to you for the science and the research. So I wanted to ask you about that. I wanted to ask you about the Adult Survivorship Program. I had just one other question about the biology that you were talking about, and that was the postpartum situation and the way the tissue, the cells change as the breast returns. You said it differently, afterwards and the changes that go on. Is that aligned with genetics, with family history? Or is what you’re describing there, that’s kind of irrespective to family history, and therefore that’s a period to be aware of, separate from the family history question?

Dr. Ann Partridge: That’s a fantastic question. And the answer is probably. Right? If you’re higher risk, then any perturbation, any change that promotes a cancer is probably going to be more likely to promote it in a person who’s higher risk because of genetic instability or inability to repair genes, which is the problem with genes like BRCA1 and BRCA2 mutations, but that has not been specifically looked at yet that I’m aware of. So these two kinds of … Different kinds of research have been looked at independently, and therefore the evolving data that mammary changes after a pregnancy, which is called involution, technically, that there’s a lot going on in the breast, and that there’s an influx of immune cells and what we call immune signature clustering that might predispose the breast cells in there to be more likely to turn into a cancer. And that probably is happening, if it’s happening, both in a person who’s not high risk, but it’s most likely … If it’s happening in people who are not high risk, it would happen probably even more in women who are high risk. Does that make sense? And there’s some epidemiologic data that this may be true. But in women who are very high risk, it may not matter whether they’ve had a pregnancy or not. Whereas it might be more likely to push someone towards a cancer, should they have had a more recent pregnancy, if they’re not high risk. If you’re following me.

Chris Riback: I am following you. Now, I know you’re looking … You’ve got nothing to do. You have no studies going on, no research, no programs that you’re running. So, there you go. There’s another thing potentially to look at.

Let’s turn, and tell me about Young and Strong. Tell me about the Young and Strong Program for Young Women with Breast Cancer. What is it? How did you create it? with others, I’m assuming. And what does it provide?

Dr. Ann Partridge: So, yes, it’s a team effort. And any of the research I’m talking about, whether I’ve been a part of it, or it’s been from the larger cancer research community, it’s all a team effort. There’s no … There are competitors, but the fact is that we all have to work together to figure this out. And from a clinical standpoint, while I love the research, there’s a lot that we already know that I realized early on patients were coming to me for a second opinion, or they were seeing a colleague who was maybe new or wasn’t focusing on young women, and they weren’t hearing about things like fertility. Or they’d come from a second opinion, and they wouldn’t have had genetic testing yet, and they were 35 years old, and it might’ve impacted on their treatment decisions. And they certainly weren’t getting, across the board, more comprehensive kind of survivorship and supportive care once they were kind of through the immediate treatment trenches.

And so in 2005 at the Dana-Farber, with support of patients and philanthropic funds and colleagues, we established this program for young women with breast cancer, which we rebranded to be Young and Strong. And again, coming from the patients saying, “Look … ” And patients have also said, “You don’t have to be strong.” And I say back to them, “That’s right, but we’re going to be here and be strong to help and support you in case you’re not strong. We’ve got your backs.” And so we created this community basically, and we’ve served over 5,000 new young patients directly in our clinic and scores of women. beyond that, I’m sure.

And we’ve been working for now over a decade to try to not only push the field forward in terms of research, but to help disseminate best practices, and best supportive care, and best, you know, “Make sure you talk to the young woman about fertility before she starts her treatment. So if she wanted to do anything to preserve fertility, make sure you plug her in with the psychosocial supports, with a social worker, or with resources in her community all along the way because each step of the way has different stressors. Make sure that you think about the aftermath for this young woman, not just when you’re talking about the risks of chemo before you have them sign the consent, but later when she’s still feeling tired, six months after she’s finished all her treatment, or when she’s feeling down, or when she’s having hot flashes, or when, she doesn’t know it, but her bones may be thinning, and you’ve got to think about bone health in the long haul because she needs to have those bones for another five or six decades.” And so this is the kind of comprehensive approach we try to follow.

And as you alluded to earlier, this is something that affects not just the patient, but the patient’s whole system. So we’ve got to think about her loved ones, her partner, for young women, if she has a partner, or her ability to partner, or her children. And so trying to kind of have a comprehensive approach to kind of total patient care and getting women to, not only live through a cancer, which of course is super important, but kind of thrive through and beyond a cancer diagnosis and treatment. And that’s where the challenges, but we’re up for it. And this program, I think has really helped more young women to cope, to find community and support and resources and better care, and we’ve tried really hard to disseminate our best practices beyond the hallowed halls of Dana-Farber and to get to not just our affiliates and satellites, but to share resources with colleagues across the country. And it’s super cool because we’ve actually developed this really nice collaboration with folks across the world.

And now every two years we meet in … Right now we meet in Lugano, Switzerland, and we develop guidelines for young women. And this is in conjunction with the European School of Oncology, which is based in Europe, obviously. And we develop guidelines for best practices, you know, “How do you distill the latest research to apply to our youngest patients?” Because sometimes people don’t know whether it should apply to the young patients. And so we sit there, a group of experts and patients and advocates sit and think about it in the context of our youngest patients. And then we publish it, so it’s available for other providers and researchers and patients to learn from and potentially impact on their care. That’s exciting.

Chris Riback: It is exciting, and it’s a really important point, I think, for any listeners or anyone really to know about. In my own learning about your efforts to prepare for this conversation, I saw it. I mean, that you’ve put together, and by you, I mean the royal you, you and colleagues, et cetera, have put together videos, slideshows, speeches, presentations, data, guidelines and more. I just think that that’s, I’m sure for you as well, that’s imperative for folks to know about. And it said to me as well that, among the many ways I’m interpreting you seeing your role … You are a researcher. You’re a scientist. You’re a doctor. You’re worried and focused on the biology. You’re worried and focused on the emotional, mental, psychological components, but you’re also a communicator. And that the communications on this is … it feels like is part of how you see your role.

Dr. Ann Partridge: Yes. And for any researcher, if a tree falls in the forest and no one hears it … And so we do need to be able to, not just share our results, but there’s a whole school of, “How do you disseminate the findings and help to implement changes in care?” And even with a hot new drug where you have a whole, usually a pharmaceutical industry pushing the drug and sales forces doing that, it can take three years for a drug to get disseminated to the majority of people. Now try and think about like supportive care approaches. It’s just so much harder. And so we, people who are working on this, need to remove the barriers and make it accessible because we don’t have sales forces. And so we need to make it kind of a priority in that … And most providers want to treat their patients better. And so, getting out there, shouting it from the hilltops, developing resources that are good for the providers and good for the patients and accessible, that’s what we’ve tried to focus on.

And personally, I’ve been very grateful because groups like the BCRF recognize that. And they support my work, that’s not drug development in this context; it’s improving survivorship care for young breast cancer patients and developing an intervention right now that is web-based, so phone, web, laptop, tablet, log on from home.

Chris Riback: Yes, all the ways we connect.

Dr. Ann Partridge: Yep, and can log on and get support in the middle of the night. That’s what we’re trying to do. And their providers can refer them to that, which helps the provider because then they’re not calling the patient … Excuse me, then the patient’s not calling them in the middle of the night or suffering, more importantly, for six months until their next follow up visit in survivorship, which is more likely to happen because a patient’s not going to page their doctor in the middle of the night for a hot flash. But if there’s a remedy for that that they could access from a trusted source, wouldn’t that be wonderful? And so that’s what we’re kind of working on.

Chris Riback: And to do be clear, and you’ll correct me if I’m wrong, but then I need to ask you about the research and two of the studies that you’re working on right now. The Young and Strong program as well as the Adult Survivorship Program, my takeaway was that those are unique programs, but there seem to be deep connection and maybe even some overlap, but that they are separate programs. Did I interpret that right, or are they kind of more closely aligned than that?

Dr. Ann Partridge: Yes. So at Dana-Farber, we have these two unique and separate programs, the program for young women, or Young and Strong, and the Adult Survivorship Program. And they are separate, but at Dana-Farber are unified because I am the director of both of them.

Chris Riback: Got it.

Dr. Ann Partridge: But the goal of the Adult Survivorship Program is to help to support survivors across the cancer spectrum. Right?

Chris Riback: Okay.

Dr. Ann Partridge: But there’s a lot of overlap because survivorship begins at diagnosis, and things like oncofertility and fertility preservation for young adult and adolescent cancer survivors is an issue, for example, that’s not unique to breast cancer survivors. It’s something that’s appropriate for all young cancer survivors from the date of diagnosis. So, there is a fair bit of overlap. And so I started to run Adult Survivorship after some of the successes of our young women’s program. And the ability to kind of scale up has  been a bit of a challenge. “How do I help the young testicular survivors?” things like that. So, we work on that. And it’s a much different scope and a larger team and very multidisciplinary, even beyond the breast cancer trenches because you have to think about all of the other diseases for that. But there’s a lot of overlap. And I think the Young and Strong Program has helped to provide some experience for how to better deliver care and how to better disseminate  findings and things that we already know within a large cancer center and then beyond to people who are not coming into a comprehensive cancer center like ours, so they’re synergies.

Chris Riback: Got it. Understood. And yes, I understand how the Adult Survivorship, it sounds like covers a range of cancers. And that’s a whole separate conversation. I have gotten so much from talking to scientists and researchers about how much gets learned in one area of cancer research or care, and then goes into an experiment or a study to try to apply it in other areas. So, makes total sense.

Dr. Ann Partridge: Right. And it helps that … I’m all against, as I’m sure you guys are, we’re against silos, right?

Chris Riback: Yep.

Dr. Ann Partridge: And it’s easy to have a silo when you’re busy and you’re focused. And so one of the things that we work on really hard is not silo-izing the research from the clinical care, right? These things have to be kind of iterative and go back and forth from bench to bedside to population. And then on top of that, I don’t want to siloize breast cancer in either direction. So, yes, we’ve separated cancer now in order to make breakthroughs, but what we learn in breast cancer, we can now sometimes move to lung and colon and testicular and other cancers and vice versa. Right?

Chris Riback: Yes.

Dr. Ann Partridge: And so that’s true from a biomedical standpoint, and it’s also true from the supportive care standpoint.

Chris Riback: So it’s important that I get to ask you about and get to learn about your research. You are launching two parallel studies that will build on prior research to improve the understanding of the complex medical and emotional problems that we’ve been talking about, the ones that face young women with breast cancer, with a new focus, as I understand it, on intervention and outreach. One of them is the “Young Women’s Breast Cancer Study Two.” And the other one I believe is titled the “Young Women’s Breast Cancer Study Two: Internet.” Tell me about each of them please.

Dr. Ann Partridge: Sure. And that has evolved. So I will say, just to clarify, we’ve kind of put them together.

Chris Riback: Ah, okay.

Dr. Ann Partridge: We’ve just completed a pilot where we have developed a web-based portal, as I alluded to earlier, that is designed to help women both report symptoms and problems and informational needs. And in the moment that they trigger and report a problem or an informational need, they are actually sent to their portal, information or support or how to manage that need or that concern or that symptom. So, it’s kind of real-time iterative supportive care. Again, you can sit on your couch at midnight and answer the survey that asks, “Do you have hot flashes?” or, “Are you worried about your sexual health?” or, “Are you’re worried about your pain or fatigue?” And if you say more than no, if you say a little or a lot, in different degrees, you will get information about how to manage that particular symptom that comes to you.

And if you don’t say anything, if you say, “I’m totally fine,” you’ll just get some supportive care things generally about what to think about and how to optimize your health behaviors and things like that. So you get something no matter what. And plus, we’re pulling people to come together to form a community within the portal. So it’s a way for other young women to connect with other young women as well as our team. And they can also do journaling because we know from other data that that can help young women to process and emotionally deal with a breast cancer diagnosis and survivorship.

So we just finished a pilot of the portal that the women can also track their symptoms over time and see if they’re improving. They can also, again, as I said, communicate with one another. And so we just finished this pilot, and it was very, very successful. Women were very engaged. We accrued women who had newly diagnosed breast cancer, age 45 and younger for this one because it’s supportive care, and women who are survivors, meaning out of initial disease treatment and kind of moving beyond. And then another group of women living with advanced breast cancer, living with metastatic disease. And we got feedback from these women. So not only did they respond to the surveys, but they also told us what they thought. We’re interviewing. We’re almost done with the interviews. And we’re interviewing them now. And we’re learning about the pros and the cons and the, “Was it wasn’t too much, or was it too little?” And, “What would help you engage more?” And this is the kind of research that you have to be very patient with because you want to hear all the criticisms, right?

Chris Riback: Mm-hmm (affirmative).

Dr. Ann Partridge: You want them to tell you what they liked, and what they didn’t, and have them be honest because you ultimately want a product that they’re going to engage with.

Chris Riback: Of course.

Dr. Ann Partridge: And so we are in the process of revising the portal right now based on that feedback. And then our next step is to launch three different initiatives, one for each of those groups that will use this web-based platform, that will now be tweaked for each of those groups. For example, in these survivors, the top symptoms weren’t nausea or vomiting. They were anxiety, hot flashes, sexual health, right?

Chris Riback: Mm-hmm (affirmative).

Dr. Ann Partridge: And so we’re not going to ask them about nausea and vomiting very often, right? Because they don’t need that information. They’re too far out. And in the metastatic patients, that actually was true too. So we’re going to … We’re tweaking things, but we didn’t know that until we surveyed them and found out that, “Nobody’s really interested in this. And people are more interested in that.” And we also found out, interestingly, in the feedback, a high proportion of people were … When we talk about survivorship, we think a lot about the kind of system issues and the patient direct issues. And one of the things that we hadn’t thought about, which I’m embarrassed to say because now it’s like common sense, is they wanted more information and support about the financial toxicity. Right?

Chris Riback: Yes.

Dr. Ann Partridge: Of course it makes sense. And yet I hadn’t thought of it. It wasn’t in there as a … They didn’t trigger that because we didn’t ask them. We didn’t ask them. We ask them, “Tell us what else you’d like to see,” in an open forum, which this is one of the things they told us both then and in the interviews. So it’s pretty cool, right? This is why we pilot this, because you’ve got to learn from your patients what do you need to deliver better and what more. So, now we’re working on adding that as well and plugging in resources, which is just hard, but they’re out there. And some of this is about connecting patients with resources.

Chris Riback: Incredible how any of us, but in this particular case people like you and colleagues who do this, have done this every day for years, talk to patients every day for years, and yet still can learn new insights and gather new data and then refine your activities or opportunities for patients to more customize it, make it more relevant and make everything just more directly useful, and the continual learning that can occur really in just about any area in life is always fascinating. And I’m sure that’s one of your takeaways as well.

I’ve got to understand. And in listening to you, how did you get into this? And I mean going back, way back. Where did you grow up? For you, was it always science? Was it always research? Or were you just on the verge of becoming a world class Olympic athlete, and at the last minute you just said, “Nah. I’m not going to do that. I’m going to do science instead”?

Dr. Ann Partridge: So I was always going to be a doctor. In fact, I tried to talk myself out of it because my wonderful father is a physician. He’s now retired. So that was kind of in my blood for lots of reasons. And yet I kind of fell into breast cancer, to be very honest, not because I necessarily needed to do breast cancer, but because I found a mentor that was a breast cancer rock star, Eric Winer, when I was a fellow. I knew I wanted to attach my wagon to his star in terms of just … I wanted to be like him. And that’s the idea of a mentor. So, and I was happy to do breast cancer because I was interested in women’s health, and I liked the long term relationships. And I also liked the evolving science that I was seeing in the early fellowship oncology trenches. So that’s how I initially started with breast cancer.

I grew up on Long Island, by the way. I’m a New Yorker by birth, but then I came up to Boston for a man. But that being said … And for my Dana-Farber fellowship.

Chris Riback: Of course.

Dr. Ann Partridge: It was a good one. But really it was about my now husband. So, fast forward though. I’m in the oncology trenches. I’m trying to figure out what I want to do when I grow up in oncology. I start working with Eric Winer. And two things happened. One is that, in the clinic, because I’m a clinical doc. I’m not a test tube researcher. I started seeing in the clinics what I described to you earlier in this, the suffering of the youngest women. I started seeing … They were just pulling on everybody’s heart strings. And I felt like we could do more for them so, and we could learn more for them. And when they’d ask questions about, “How likely am I to go through menopause with this chemotherapy?” We didn’t have enough answers.

And so that’s where I found my niche clinically and thought, “Hey, this is an unanswered area. I could dive right in here because it’s both fascinating to me, and I could do good, and there’s room.” And so for me, that was kind of what hooked me. And then I will tell you, when I was about 29, and my best friend was 30, I got a call from her, my best friend from high school. She had a lump. She was in New York, actually. And fast forward. It ends up being breast cancer. And fortunately, her survival was actually not the thing we were worried about.

But I heard from her from the inside, from … She shared with me things you don’t share with your doctor typically, but what you share with your best friend, which is, “How do I deal with one breast, and the shirt I want to wear on Friday night?” I have this new partner. And how do I deal with that from an intimacy standpoint? Can I have a baby? Or is that not going to be safe?” And then we weren’t sure whether it was safe. Now we’re pretty sure that it is probably safe to have a baby after breast cancer based on available evidence. But at that time, we didn’t have enough data to even answer those questions, or enough resources to answer kind of the beauty and self-image stuff. And I heard from her kind of firsthand, how hard it was, even when it wasn’t about surviving the cancer. It was really about kind of moving on.

And so for me personally, that made me even that much more interested in the supportive care stuff, the softer stuff that the doctors and even the nurses, quite frankly, don’t pay that much attention to, and yet are so important for the day to day for our patients that we kind of should help them with this. And so we’ve tried to build ways to help them better, in partnership with other groups, with advocacy groups, and with duty groups, and with all kinds of good partnerships where we all want the same thing. We want people to look and feel good, right?

Chris Riback: Yep.

Dr. Ann Partridge: And so that’s kind of been an area … That’s where it came out of. That’s where … For me, it was, “Okay. This is a good fit for me, and my personality, and my mission.” And that’s how I’m here.

Chris Riback: That’s an incredible series of inputs in both the personal and the professional … Yes, I mean those conversations with your girlfriend. As well, I can say I had the great privilege of doing one of these conversations with Dr. Winer. And so, I get it. You were fortunate-

Dr. Ann Partridge: You met the rock star.

Chris Riback: I got to talk to the rock star, yes. So, yes, I get it. If you had the opportunity … If one had the opportunity to work with him, I can see how that could be life changing and could really help direct a career, which I am willing to bet you have either passed forward and passed on, or will. But my guess is you likely already have too many folks. So, thank you. Thank you for that. And thank you for taking the time with me today.

Dr. Ann Partridge: Oh, it was a treat. Thank you.

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It’s something we all think about every day: What should I eat? It’s a question that Dr. Walter Willett thinks about every day.

A BCRF investigator since 2001, Dr. Willett’s research has aimed to characterize the impact of diet and lifestyle on health outcomes, especially in relation to breast cancer risk. His current studies focus on the effects and protein sources on breast cancer risk and finessing the tools used to analyze dietary intake.

Dr. Willett, Harvard Medical School, is a global leader who focuses on the intersection of diet, lifestyle and health. As the most cited nutritionist worldwide, his work has influenced numerous health recommendations and continues to inform preventive strategies for breast cancer. Dr. Willett is Chair of the Department of Nutrition at Harvard School of Public Health.

Read the transcript below:

Chris Riback: Dr. Willet, thanks for joining me. I appreciate your time.

Dr. Walter Willett: Thank you, and glad to be with you.

Chris Riback: Before we get into the science, I’d love to ask you about timing, because you seem to have timed your career about as perfectly as anyone I’ve come across. Your initial studies into diet, lifestyle and disease began really in the 70s and early 80s, I guess, with the Nurses’ Health Study 1, and various follow-ups and work before that and obviously new studies in the decades since. But your work timed perfectly, as far as I can tell, with the explosion in our popular culture around those very topics: lifestyle, diet and disease. Should we just cut to the end and go ahead and claim that you are personally responsible for this cultural phenomenon, or did it just so happen that your area of scientific research intersected perfectly with the times?

Dr. Walter Willett: It would be overstating it to say I’m responsible for the current interest, but in fact I’ve been interested in food since I was under 10 years of age, and I learned how to milk a cow when I was four years of age. So, food has been part of my interest for a long time. I grew vegetables to put myself through college and studied food science … went to medical school. I was fortunate in the sense that all of these pieces of my background have proved to be very useful when the interest emerged in diet and health.

Chris Riback: Was it kind of emerging when you … I mean, you studied, as you said, food science. Was the … how strong was the research and kind of the general interest at that time as you were getting into it, into that intersection between what we eat and who we are, how we live and who we are? Bring me back to that time a little bit. I realize I was being facetious in hinting that perhaps you invented it, which I know, but what were those times like?

Dr. Walter Willett: This really goes back, I think, to the 1960s when there were some early, very simple, crude kind of studies, but that were important in stimulating research. They were what we call today ecological studies, looking at rates of major diseases like breast cancer and heart disease in various countries around the world, and what those studies showed was that there were huge differences that were first really well documented in the 1960s. Rates of heart disease varied tenfold across Northern Europe and Southern Europe and about eightfold for breast cancer between Japan and the United States.

And then some other very simple, but really critically important, studies showed that people moving from low incidence countries like Japan where breast cancer rates were very low to the United States eventually adopted … it took a generation or two, but eventually adopted rates of breast cancer and then heart disease that were really similar to European Americans living in the United States. So, those really profound basic observations fueled a lot of interest. People said, “Why? What is there about living in the United States or other western countries that leads to such high rates of heart disease and breast cancer and other conditions similar to those diseases?”

Dr. Walter Willett: And that really … those data were emerging in the 1960s, 1970s and then I went to medical school. I, during that time, got more interested. We were faced with people with cancer and heart disease and almost nobody was asking why someone had breast cancer, why someone had heart disease. That kind of question bothered me and got me interested in trying to understand the basic origins of these conditions. So, this was a good time, and I was fortunate that a lot of my background had prepared me to take on some of those very complicated, challenging questions.

Chris Riback: And what were the reactions in the scientific community when you started to ask why?

Dr. Walter Willett: Well, first of all, there were some indicators that diet might be important and that’s because there were correlations if we looked across countries with higher fat intake did have higher rates of cancer and higher rates of cardiovascular disease. But epidemiologists in general knew that there could be other factors that were correlated with, say, fat intake that were the real causes, other aspects of diet, smoking, physical activity. And so we really had to look more deeply. When we started to look at diet, the conventional wisdom was you can’t study that within the United States population because everybody eats the same. But it didn’t take us very long when we started collecting data, we realized that not everybody ate the same. There were huge differences in people’s diets and therefore we had an opportunity to identify the factors that might be important, or not important, for breast cancer and other conditions.

Chris Riback: Why are nutrition-based studies so challenging? You just mentioned or hinted at one aspect of doing a study, which is focusing on self-reporting of what people eat, and maybe you didn’t actually say self-reporting, you said when we discovered what folks eat. But there’s a self-reporting component, or at least there was historically, but that has evolved. Take me through the science behind nutrition-based studies. What made them historically challenging and what makes them potentially challenging today?

Dr. Walter Willett: Nutrition studies are challenging when we’re looking at long term consequences, like risk of breast cancer, and part of that is related to the origins of breast cancer and many other diseases themselves, because these are diseases that don’t just pop up overnight. As we dig more deeply, we see that the origins of these diseases … excuse me, one second … we see that the origins of these diseases often are many decades before the condition is actually diagnosed, so to understand the causes we’re going to have to do studies that last for many decades.

Dr. Walter Willett: Second, diet itself is very complicated, that probably no two people eat exactly the same diet. We can look at it on the basis of foods. We can look at it as nutrients, and these different dietary components are often correlated. They’re usually correlated with each other, so pulling them apart is challenging. There also is no simple biochemical test, blood test, for defining someone’s diet. For example, just to take something as extreme as sodium, the body regulates sodium intake very, very precisely so the blood test tells us almost nothing about sodium intake, even though we can measure sodium in the blood.

Dr. Walter Willett: So, for many aspects of diet we do need to rely, at least up until this point in time, primarily on individual reporting of what they ate. And one of the other challenges to doing these kinds of studies was that skeptics would say, “Well, I can’t remember what I ate for lunch yesterday. How can people possibly report what they ate?” But the fact is, we’re not really interested in what someone ate for lunch yesterday. We’re interested in what they usually eat over the longer term. And as we’ve studied this, we do see that people can report their intake reasonably well. Not perfectly, but reasonably well.

Dr. Walter Willett: For example, some people, if we’re studying milk, that’s been a great interest, there are many people that have three to four glasses of milk a day. Others have none at all, and a lot of people in between. And we can ask how often people have a glass of milk, and it’s not very hard to separate people. Those people who have three or four glasses a milk a day can easily identify themselves, especially when we contrast them to people who consume almost no milk in their diet. And with standardized questionnaires, we’ve found that people’s report actually does correlate quite well with biomarkers of intake, for example. We can see that blood levels of carotenoids do correlate quite well with people’s reported intake of fruits and vegetables that are high in carotenoids.

Dr. Walter Willett: So, there are definitely challenges. There will never be a perfect study, and we have to accept that. The perfect study would probably be too randomized. Children, when they’re born to diets high in carrots or high in milk compared to low in milk, and follow them for the rest of their life, and of course we can’t really do that. And now we’re even learning that the mother’s diet is likely to be important as well. So, we’re not going to be able to do a perfect study but we can look at pieces at a time and put the whole package together to see the picture, the total picture, even though we can’t do the perfect study.

Dr. Walter Willett: As we go on in time, that picture becomes clearer, with bigger studies, longer follow up, better measurements. The picture becomes sharper with time. So this is a long process. We’ve learned a lot, actually, in the last few decades, information that we didn’t have when we started off in the 1970s. But there’s still additional, many details to learn.

Chris Riback: It’s remarkable how many hundreds of thousands of people you and others have been able to … follow might be a little bit too specific, but have had as part of your studies for so many years, I guess beginning with the Nurses’ Health Study, the first one, which I think launched in 1980 or certainly the very early 1980s, that the range of inputs on data that you and other scientists and researchers must have just seems … it’s kind of incredible. I want to ask you about some of the specific work that you’re doing around not just breast cancer but specific types of breast cancer.

Chris Riback: To get into that, perhaps the broadest question that I’m going to ask and too broad so forgive me, but I’m hoping to use it as a launching point into the more specific studies. What would you characterize … what do we know about diet, lifestyle and cancer?

Dr. Walter Willett: We have learned, first of all, that this is a long process, that what you eat today doesn’t affect your cancer risk tomorrow. What you were eating as an adolescent probably does affect breast cancer risk many years later, so we have to have long term studies. We have … probably the single strongest claim to emerge is that overweight and especially weight gain during adult life is a major risk factor for many types of cancers, and I think a lot of people just take that as a matter of fact today. But 20 years ago, that actually wasn’t appreciated. Actually obesity and overweight are almost equal to smoking as a cause of cancer when we look at a total population on an individual basis. Smoking is definitely worse than being obese, but since we have many more people who are overweight and obese than we do people smoking today, the total number of cancers caused by overweight and obesity is actually about the same as the number caused by smoking.

Dr. Walter Willett: We’ve also found that some choice of foods does make some difference for cancer. The poster child of nutritionists for many years has been fruits and vegetables, and there was some clear overstatement about the potential benefit for cancer reduction of fruits and vegetables. But as data have come in, we have seen that particularly ER-negative breast is related to … associated with low intake of fruits and vegetables, so there is some payoff there, especially for some of the most aggressive forms of breast cancer.

Dr. Walter Willett: High consumption of red meat at various times of life is related to several cancers. And even moderate alcohol consumption is related to breast cancer. That was a finding that was very controversial when we reported it back in the 1980s, but that’s been confirmed in dozens and dozens of studies now, and is an accepted risk factor for cancer. So, that’s a quick overview of some of the key findings that have emerged for cancer risk, and overweight and obesity is clearly the biggest part of the picture.

Chris Riback: That’s a pretty good answer to about the broadest question I could possibly ask, so let me try to home in a little bit. As I understand it, your work now will examine the relation of dietary factors to the risk of specific types of breast cancer. You’ve talked about this a little bit so far in the conversation. Including tumors characterized by HER2 status, histology and stage, how does … describe for me if you would the work that you are doing now and how does this differ from your previous breast cancer work?

Dr. Walter Willett: Let me just take a step back there. For a long time, we’ve really considered breast cancer as one disease. Early on clinicians did learn that different forms of breast cancer mainly characterized by being estrogen receptor positive or negative responded differently to treatments and therefore the treatments were personalized, we might say in today’s language, to ER negative versus ER positive.

Dr. Walter Willett: Early on in our breast cancer studies, we didn’t really have a chance to separate these forms of cancers because we didn’t have enough cancers to look at those separately. But as time has gone on in our studies, we now have in fact in our large cohort studies almost 20000 women have developed breast cancer and we’ve been able to get medical records with the receptor status documented, or we’re now collecting tumor samples and actually analyzing the cells for receptor status and other tumor characteristics. And we do find that risk factors for estrogen receptor negative first, and estrogen receptor positive breast cancers are different, so it is really important to study these separately.

Dr. Walter Willett: And as time has gone on, of course we’ve learned about other characteristics of breast tumors and we’re essentially characterizing the cancers that develop in our large studies by these other features, and that provides quite a bit more power to identify risk factors. If we lump them all together we can miss some important relationships.

Chris Riback: How will this research occur? What’s the process? Do you leverage existing people and existing data that are already in your cohorts, and you will just look at that data differently or through different lenses? Or do you need to build a new group, or do you add a new group and compare that to a historical group? How will the research work for you? Or, how is it working for you?

Dr. Walter Willett: For the most part, we’re leveraging the information that’s already available, that we’ve been collecting since 1980. Since that time we’ve enrolled about 200,000 women. I should mention they’re all registered nurses and the success of these studies really has been dependent on the incredible commitment to being in research on the part of these nurses. Almost 90% who are still alive are still participating almost 40 years later. The information we have on diet and lifestyle and hormones and physical activity, other lifestyle factors that’s in our computer that has been accumulating since 1980 is really invaluable. You can’t buy that kind of information … when we want to look at types of breast cancer.

Dr. Walter Willett: So starting all over would be a very big step backwards. We’d have to wait decades before we had the answers. So, about 20 years ago we did ask … started asking women in our study for permission to get samples of their breast tumors, and we’ve been collecting those samples. In the early years we were just storing them. We now have tumor samples from about 9,000 participants. And more recently, we’ve been sampling each one of those tumors and making what we call micro arrays. So on a single slide, we can put samples of several hundred breast tissues, and then we work with our collaborating pathologists, who are experts in essentially identifying characteristics of these tumors using a variety of methodologies, some analyzing DNA, some analyzing different proteins in the tumors, and that allows us to identify the subtypes of breast cancer.

Dr. Walter Willett: We are also starting Nurses’ Health Study 3, but information from that won’t be available, results won’t be available for several decades down the road. So, we’re essentially piecemeal-ing various birth cohorts of women over time to learn about these important relationships. But the basic process here is using new technologies, applying the latest developments in genetics, metabolomics, microbiome and pathology to tumor tissues that have been accumulating in our cohorts’ first several decades.

Chris Riback: Wow. And Nurses’ 3, is that group the same initial age group as Nurses’ 2 and Nurses’ 1? I think that those were kind of in the age 20 to 32, was it? Or 35, something in that zone for when the nurses came into the studies? Is it the same for Nurses’ 3?

Dr. Walter Willett: In general, yes. One of the really important general findings we’ve found for breast cancer is that the origins are often in earlier life. And in the first Nurses’ Health Study in 1980 they were 34 years of age when we first collected dietary data, and we wanted to look at younger years so we started off as young as 25. That’s been very helpful because we could do two things, we could … enough of their mothers were alive we could actually ask their mothers, and about 40,000 mothers responded, described their pregnancy with the nurse who’s in our study and their breastfeeding characteristics, early life feeding characteristics, their weight gain during the pregnancy. So we do know a lot about our nurses even when they were in utero.

Dr. Walter Willett: And then we could also, when they were still young we could ask in retrospect about their diets during high school years, which we found to be particularly important. And one of the clues about that period of age was that in the American atomic bombing of Nagasaki and Hiroshima in Japan, if women experienced radiation exposure during those early years, a few decades later their breast cancer rates jumped up. But if they were over 40, there was almost no increase in breast cancer risk when they were … due to radiation exposure. So it really did point to early life being important, and it’s turning out that what people eat, what girls eat during high school, does make an important difference in their future breast cancer risk. So that’s why we’ve been going to earlier years.

Dr. Walter Willett: That’s not to say that everything is cast in stone after those years. We still see that changes in behavior, especially changes in weight even up into the 50s and 60s can make an important difference in breast cancer risks, so we really need to look at the whole life span.

Chris Riback: So I could imagine somebody listening to this right now and saying, “Okay, doc, I’ve got a daughter, she’s a teenager. You just said that early life and early diet and lifestyle matters. What should I tell her to do?”

Dr. Walter Willett: Well, having had a couple teenagers at one point in time, just telling them what to do maybe … doesn’t always produce the responses we would like, but-

Chris Riback: No, it doesn’t. In fact the recommendation might be not that this is what I say to do but this is what Dr. Willet says to do. So no one will … we’ll all blame it on you.

Dr. Walter Willett: Right, yes, blame your doc. Somebody else, that’s for sure. But still, we should convey information to our kids growing up and more importantly, we should provide to them healthy choices and encourage them in every possible way that we can, including making them attractive and interesting. For the specifics, we have seen that high consumption of red meat is related to higher risk and emphasizing more plant bases of protein sources is related to lower risk and that higher intake of fruits and vegetables and whole grains is related to lower risk as well.

Dr. Walter Willett: In general, this does fit a Mediterranean-type dietary pattern that’s got a lot of variety. It’s not vegan, necessarily, but emphasizes more plant-based protein sources than animal-sourced foods. So that’s the general picture of what we’re seeing, and as time goes on we hope fully we’ll be able to define some of those characteristics of a healthiest diet even better.

Chris Riback: What about the relation between diet and lifestyle and the survival from breast cancer?

Dr. Walter Willett: Until quite recently, we’ve been mainly focused on looking at aspects of diet and lifestyle that could prevent breast cancer. But now with long follow up after multiple decades in our cohorts, we’ve been able to look at aspects of diet after diagnosis of breast cancer and how that relates to survival from this serious disease. That’s taken a long time because we, in our research, first want to have a diet before breast cancer and someone develops breast cancer, then we collect the data after diagnosis of breast cancer, what people eat, the physical activity and other information.

Dr. Walter Willett: And then we start follow up, looking at survival. And we know that for breast cancer the risk remains elevated for two or three decades, at least, after the diagnosis, and that does offer an opportunity to potentially modify our diet and other lifestyle patterns. Our information is just starting to emerge from this follow up looking at survival. We do see that an overall healthy dietary pattern, we might call it a Mediterranean dietary pattern, is related to better overall survival, and right now we’re actively looking at more detail, at pieces of the diet, and how they can be important in improving survival. We’re hoping to have some pretty firm results over the next year or two in that regard. This is quite an exciting new area, and I think we’re going to have some answers.

Chris Riback: This is just coming to me as I’m listening to you, so this may be a wrong way to think about it, but is there any … so, when I think about smoking, I think okay, the correlation … as a lay person, the correlation between smoking and lung cancer has to be … that’s got to be really strong. And obesity, you mentioned, and so obesity with heart disease, or smoking with heart disease. I think I know, as a layperson, from having read popular culture that there are things that one can do in one’s life that really impacts those diseases. Colon cancer, perhaps, with what I’ve heard about red meat, and if any of this is wrong you’ll correct me on my facts, because I’m just going off of my general understanding.

Chris Riback: Where would breast cancer … is there any way to think about the strength, which may not be the right word, but the strength of the inputs into the negative effect of breast cancer, meaning I know that if I smoke the negative effects resulting in lung cancer has got to be pretty strong. I don’t know the science exactly, but I know from life that that’s got to be pretty strong. Are the inputs, dietary lifestyle, can it be correlated as strongly with breast cancer or is it more complicated, we don’t know as much? And if the question has just kind of confused the issue totally, then feel free to just set me straight.

Dr. Walter Willett: Breast cancer is definitely more complicated than diabetes and heart disease in terms of the causal factors, and how they operate over time. And for example, for smoking and lung cancer we can see if we eliminated smoking, we would reduce lung cancer by about 90% from what it was a few decades ago. In fact, we’ve already made a lot of that reduction, so further reductions are not going to be as great since most people are not smoking now. And for heart disease we can … if somebody’s smoking, they can cut their risk of heart disease by about two thirds by not smoking.

Dr. Walter Willett: The relationships between risk factors and breast cancer are not nearly as strong. Probably the strongest lifestyle factor is waking during adult life in relation to breast cancer after menopause. And breast cancer … one of the examples of why breast cancer is so complicated is that actually being overwinter as a young child or adolescent is related to lower breast cancer risk, not higher breast cancer risk. That is one of the reasons why a lot of women who are struck with breast cancer when they’re 35 or 40 say, “How can that be? I did everything right?” And they’re correct. This is an enigma. We have some clues about what might be explaining that, but we still don’t totally understand this really unusual finding of cancer rates being lower with higher obesity.

Dr. Walter Willett: But weight gain during adult life is related to breast cancer after menopause, so it’s that adult weight gain that’s really important. And that is moderately strong. We see that women who gain quite a bit of weight can about double their risk of breast cancer after menopause by doing that, or conversely, avoiding that weight gain can reduce the risk by about half, compared to what it would have been with gaining a lot of weight. That’s pretty typical in the United States.

Dr. Walter Willett: When we start putting together multiple risk factors, we can see, for example, that weight gain in combination with use of hormones explains about half of the breast cancer incidents, or mortality, in the United States. In other words, if almost no women use hormones after menopause and did not gain weight, breast cancer rates would probably be about half of what they are. And interestingly enough, in Japan, very few women have used hormones after menopause and quite amazingly Japanese women, on average, do not gain weight during adult life. If anything, they slightly reduce their weight during adult life. So those two variables explain about half the difference. So we’re seeing some important pieces, but they’re not as strong and they’re more complicated than lifestyle factors in relation to lung cancer or cardiovascular disease.

Chris Riback: What role has BCRF played in your research?

Dr. Walter Willett: BCRF funding allowed us to start the cohort of about 25,000 offspring of our Nurses’ Health Study 2 when these kids were 10 to 14 years of age, and that’s really still the largest cohort now of adolescents who were enrolled during that period of life and where we have a lot of dietary and other data. These children are now in their 30s and we’re already being able to look at diet and benign breast disease, and down the road we’ll be able to look at breast cancer itself.

Dr. Walter Willett: So the NIH funding was just not fit for that kind of study. They want answers within five years, but we know that long term investments in research are really critical if we’re going to understand the real origins of this disease. There are many other areas where BCRF funding has been critical. It allowed us to start collection of mammograms from participants in our study, and that’s a whole new direction that’s opened up. Actually, abnormal mammograms are the strongest risk factor we have, one of the strongest risk factors we have for breast cancer. That’s been an important aspect of our research.

Dr. Walter Willett: We’ve been able to do pilot studies that in the longer run gave us … allowed us to get funding for NIH research. It’s helped us develop the world’s, really, most comprehensive data base on the biochemical constituents of foods that we update every four years. There’s no other database in the world that has done that over a long period of time. So in many ways, BCRF funding has been critical. But it’s not just the funding that BCRF has brought us together … I’m speaking of our whole group of colleagues funded by the BCRF that come from many different fields, clinical areas, biochemists, pathologists and many other areas. Getting together and exchanging ideas has been an important part of the support BCRF has given as well.

Dr. Walter Willett: And then finally, just the fact that there are so many people, so many women out there who are actively contributing to research on breast cancer has been an inspiration for us that keeps us going, working into the night, working weekends to take on this really serious challenge.

Chris Riback: Well, that’s terrific. In that case, I ought to let you get back to work. Thank you, thank you for your time and thank you for the work that you have done over decades.

Dr. Walter Willett: Well, my pleasure and please give my thanks to everybody who has helped make this possible.

Chris Riback: That was my conversation with Dr. Willett. My thanks to Dr. Willett for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.

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Today, we have an outstanding and thoughtful conversation on stress, breast cancer, and the science of survivorship. We all, of course, experience stress, work, family, money, but what about health, in particular, cancers like breast cancer? Obviously dealing with illness, indeed dealing with ongoing treatments and procedures brings stress to a whole new level.

How can women undergoing breast cancer treatments manage that stress? Perhaps more significantly, are there scientifically researched and proven approaches that not only help increase their health and wellbeing, but even improve the recovery process and results?

This is the important work that Dr. Annette Stanton does. Dr. Stanton, recipient of the ANN INC. Award (a division of ascena retail group inc.) and a BCRF researcher since 2004, is Professor of Psychology and Psychiatrist Bio-Behavioral Sciences at UCLA. She’s also a senior research scientist at the UCLA Cousins Center for Psychoneuroimmunology and a member of the Center for Cancer Prevention and Control Research in the Johnson Comprehensive Cancer Center.

Read the transcript of the conversation below:

Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation, in conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship, and metastases.

Today, we have an outstanding and thoughtful conversation on stress, breast cancer, and the science of survivorship. We all, of course, experience stress, work, family, money, but what about health, in particular, cancers like breast cancer? Obviously dealing with illness, indeed dealing with ongoing treatments and procedures brings stress to a whole new level.

How can women undergoing breast cancer treatments manage that stress? Perhaps more significantly, are there scientifically researched and proven approaches that not only help increase their health and wellbeing but even improve the recovery process and results?

This is the important work that Dr. Annette Stanton does. Dr. Stanton is Professor of Psychology and Psychiatrist Bio-Behavioral Sciences at UCLA. She’s also a senior research scientist at the UCLA Cousins Center for Psychoneuroimmunology and a member of the Center for Cancer Prevention and Control Research in the Johnson Comprehensive Cancer Center.

Through research, Dr. Stanton identifies factors that promote or impede psychological and physical health in adults and couples undergoing chronically stressful experiences with a focus on the experience of cancers of the breast, pancreas, eye, and lung. She then translates her findings into action by developing and testing approaches to enhance psychological and physical health over the course of the cancer trajectory.

In recognition of her research contributions, Dr. Stanton received the Senior Investigator Award from the Society for Health Psychology of the American Psychological Association in 2003. She was elected to serve as president of the 3000 member society in 2012 to ’13. She also has received the Society of Behavioral Medicine Cancer Special Interest Group Award for Outstanding Achievement in Behavioral Medicine and Psycho-Oncologic Research, as well as the Outstanding International Collaboration Award from the International Society of Behavioral Medicine. This November, she will receive the International Society of Behavioral Medicine Distinguished Scientist Award. She’s been a BCRF investigator since 2004.

Dr. Stanton, thanks for joining me.

Dr. Annette Stanton: Thank you.

Chris Riback: In so much of medical conversation and news, and not just with breast cancer, but even more generally, we focus on the scientific breakthroughs, the new treatments or the medications or the procedures. Obviously it’s incredible and wonderful and we’re grateful, but in reading about your work and your approach, focusing just on that hard … I don’t mean to call that hard science. You’re dealing in hard science as well, but just focusing just on the new medicines and the new breakthrough, that may not be enough in seeking to maximize recovery. Is that right? Am I interpreting that correctly?

Dr. Annette Stanton: Yes, I think that’s right mostly. I think it’s right in that anyone who knows what it’s like to go through breast cancer themselves or in a loved one knows that the experience and recovery are really far more than the mechanics of diagnosis and treatment. It’s the psychological experience of being diagnosed with a serious disease that could threaten your life and your goals in life. It’s going through treatments that can rob you of your energy and affect your ability to think.

It’s the effects on the people who love you and how you interact with them. It’s really also how to move on in your life once your primary treatments have ended. So, all of those are important parts of the experience that really deserve attention too, and that’s where the science of survivorship comes in.

The attention in the media and the scientific community on effective prevention and treatment and cure of breast cancer and other diseases is really well-placed. I mean, we all want a solution to breast cancer. The ability to live well after diagnosis also deserves a lot of attention.

Chris Riback: The phrase, “The science of survivorship,” how does that get integrated? How do you find does that get integrated? I mean, I read about what you’re doing and I read your materials and I think about it and I’m like, “Wow, this is exactly what I would think I would want or what anyone would want,” because what you just described about the stress and the emotional and psychological impact is extraordinary. We all would be incredibly sympathetic towards that.

How does the science and the tactics and the approaches around what you are talking about, how does that get implemented? Is that through the caring physicians themselves? Is it through other programs? How does that type of awareness and the science of survivorship, how does that become part of the recovery process?

Dr. Annette Stanton:     Well, I think there are two questions there maybe. There’s how the-

Chris Riback: There actually might have been about 10 questions in there, but you’ll go through them, I’m sure.

Dr. Annette Stanton: Let me choose two of them.

Chris Riback: Choose the best two.

Dr. Annette Stanton: I think the science of survivorship gets integrated through, really team science. I have multiple collaborators. I have mostly oncologist collaborators because most of the science that I do gets conducted through the breast cancer clinic or the oncology clinic, and so I’m collaborating with the oncologists who work in that way.

The application of the science of survivorship also can get translated through the clinic, and so when we find something that we think is really important and can help improve quality of life and health, then we work to translate that science into approaches that women can use in their daily lives. That may be translated through the clinic. It may be translated through the internet, and so really both the science and its translation into intervening, it takes a team. It takes the acknowledgement I think on the part of the team that survivorship is really important.

Chris Riback: You know this theme that you’re talking about right now has been coming up in a number of conversations, the translational aspect of science in both the research component, but also then with the learnings and the applying that and the approaches.

So, I appreciate your having broken down my question into two. Let me attempt to break your response down into two, as well. Let’s break it out into the science one, and then two, I really want to get into the approaches and particularly, the work that you’ve done around identifying, my word would be virtual cohorts or support groups, but I know some of the online work that you’ve looked into, as well.

Talk to me about the science. You’re working on multiple studies, or certainly have worked on multiple studies, that seek to identify the factors that can improve the outcomes, the quality of life after a breast cancer diagnosis. What do those studies look like? How do they work? If you want to pick either the most recent one or one of the ones that stand out in the past, just talk to me about how those studies work, please.

Dr. Annette Stanton: Sure. We use, I would say three basic methods to try to understand factors that predict quality of life and health for people with breast cancer. The first is really focused on understanding whatever subject we’re studying. There, we’re usually using longitudinal studies. So, those are studies in which we recruit women typically from the clinic, but sometimes through the media and other outlets, and we follow them over time to try to understand what factors help and hinder them as they go through particular phases of the cancer trajectory.

So, that might be immediately after diagnosis and through treatment. It might be that post-treatment phase, what we call the reentry phase when you’re finished with maybe your primary treatments, chemotherapy, surgery, radiation. It might be understanding the experience of women with metastatic disease. So, part of what we do is following women across time to understand what factors help and hinder them through the course of whatever phase we’re studying.

A second approach is to bring women, or sometimes these are studies that are experimental studies that are not specifically with women with cancer, but we’re looking at basic processes. So, we try to bring women into the lab and others and conduct experiments to understand the processes.

For example, one of our findings is that women who actively accept their diagnosis, actively accept that this is what they have and this is what they need to deal with, those women do better over time with regard to having fewer depressive symptoms and other kinds of outcomes than women who really try to push the whole experience out of their heads and out of their hearts, so women who avoid.

We also find that women who actively express themselves in terms of their emotions do better in terms of those outcomes. So, we bring, for example, women into the lab and have them write about or vividly describe their experience in particular ways, so we might have them write about their deepest thoughts and feelings about their experience, versus, for example, just the facts about their breast cancer experience. That’s in an experimental way, we use basically random assignment to understand then the outcomes of those different ways of approaching the experience.

Then, third, out on the community, we conduct randomized controlled trials to translate our findings into approaches for intervening that might help women, them for example be able to approach their experience actively through acceptance and through emotional expression and through other helpful methods of coping. So, we basically go from sort of the field to the lab and back again trying to first understand the experience, and then translate the findings. Does that makes sense?

Chris Riback: It makes total sense. What kind of blew me away is I guess the bottom line point is, the studies show that your trials and research have shown that those tactics translate, sorry to use your word, into actual results. You see positive results from women or survivors or people undergoing treatment who actively take those emotional psychological measures and approaches and tactics as opposed to, unfortunately, women or recovery individuals who don’t have that opportunity, for whom that’s not part of their process. Is that right? There’s just a tangible positive result out of these tactics.

Dr. Annette Stanton: Yes, I do think it translates into concrete results. One prominent example that I can think about that was supported in part in BCRF we called Project Connect Online. I got this idea really from women with breast cancer.

One woman who was in one of my research studies told me about the time when she was first diagnosed with breast cancer and her sister, who was an executive in a tech company, created a website for her to basically communicate on how she was doing through her diagnosis and cancer treatment to her loved ones. Many of them were far away. They were across the country. So, this kept them [inaudible 00:14:36] of how she was doing. She posted a photograph with her with no hair because she had gone through a chemotherapy that made her lose her hair. She posted photos of her doing activities that she loved, despite what she was going through.

Then, when the tech executive also got breast cancer, her sister, the first diagnosed, was well enough that she could create a website for her. So, they ended up creating websites for each other. The woman who was in my research told me how useful that was in being able to communicate with their network in a really personal way that really relieved them of the need when they were going through treatment and really tired and had sort of minimal resources that they really wanted to use on particular things, that they didn’t have to tell the story repeatedly.

It kept their network up on what they were doing and how they were doing. It told their network what they could use at particular times. For example, whether it was something concrete, like one woman’s son being brought to his guitar lessons, or, “I can really use your cards and prayers this week.”

So anyway, that conversation with that woman ended up launching Project Connect Online, because even at that time, there were some sources, one is called Caring Bridge, where people with cancer or other diseases can post to a network, the people who love them, their friends, their family, coworkers, how they’re doing with whatever disease they’re going through. So, there were some sources out there and I knew that people were communicating online, but as far as I knew, no one had tested the effects of those sources using those sources on how women did.

So far we’ve done two trials of Project Connect Online. I work with a web developer, and basically, we randomly assigned, like the flip of a coin, randomly assigned women in this first trial and this was with any woman diagnosed with breast cancer, regardless of stage, time since diagnosis, et cetera, to either have their usual care, and we provided them with some resources for contact if they needed psychological or wanted psychological resources, that sort of thing, or assigned them to Project Connect Online, which in a three hour workshop, at the end of the three hour workshop, basically they had created their own personal website to communicate with whomever they chose.

They could be very selective. They could keep it to their immediate family or they could keep it to their friends, et cetera. They had created their own personal website to communicate with others about their breast cancer experience. Lots of people would call these blogs. Really, what they became is sites to write about their experience and to communicate with their loved ones.

So, we tested Project Connect Online first against standard care in an experiment and found that the women who had engaged in Project Connect Online and who had created websites and shared them with selected others, those women were less likely to have significant depressive symptoms. They had a decline in loneliness. They had an increase in the social support they perceived from friends. They had an increase in their appreciation of life, the value they felt they got from life, and some other outcomes. So, those are the kinds of tangible results. Oh, and they got an increase in confidence for how they were coping with cancer, and so those were the kind of tangible results we got from the women.

Then, in that first study, we also asked people who visited their websites, so their loved ones, friends, et cetera. First, we found that it was mostly friends who visited their websites and we found that the friends also reported that they got a lot of benefit from understanding what the women were going through, from keeping up on their treatment, those sorts of things.

also reported that they were likely to do what the woman had asked for on her website, bring a meal or write her a card, those kinds of things. That’s one example of some of the kinds of benefits that we think are important as women go through the cancer experience.

Chris Riback: It’s such an incredible example. I mean first of all, for the women themselves, noninvasive, no after effects, no side effects, no negative side effects. I guess a lot of positive after effects, but you know what I’m saying, no negative side effects, and then that network effect that you just mentioned, which I would imagine … I was trying to think about this in terms of … And I was kind of thinking about a question for you, but it felt a little bit inappropriate. I was going to ask you about, well, gosh, your work, how do you think about … Look, when someone goes through breast cancer, they’re not going through it alone. Well, one hopes they are not going through it alone.

Dr. Annette Stanton: Exactly.

Chris Riback: There is, in theory, and usually family members, loved ones, friends, and they feel emotionally about the situation obviously, as well. So, you just described, there’s a positive network effect as well. It’s incredibly powerful. You said you had done two studies on that. I found I think one of them, the one that you published in 2013. I don’t know if that was the first of the two that you published, but that was the-

Dr. Annette Stanton: That would’ve been the first, yes.

Chris Riback: Okay, great. That’s what I thought. You’re based at UCLA, so you’re really in tune with how Hollywood creates titles, and I think that you just came up with a real Hollywood title here. Project Connect Online: Randomized Trial of an Internet-Based Program to Chronicle the Cancer Experience and Facilitate Communication. So, that may not be Spielberg’s title.

Dr. Annette Stanton: No.

Chris Riback: No, but you’re in academics, so it’s a great title for what you do for a living. What was the reaction to the study? I mean, you’re in ground and territory that I could imagine a real mixed reaction to. I could imagine some in your world saying, “Holy cow, that is so incredibly positive to find noninvasive, non-intrusive, low cost positive ways to impact people’s lives,” and perhaps, and I’m wondering this, are there others who said, “Come on, Stanton. That’s hocus pocus”? What was the reaction your study?

Dr. Annette Stanton: Well, let me first comment on some of the reactions of the people in the study.

Chris Riback: Please. Those are really the ones that matter, obviously.

Dr. Annette Stanton: You mentioned the network effect, so let me comment a little bit on that.

Chris Riback: Please.

Dr. Annette Stanton: One of the most meaningful notes I’ve ever had about my research came from a daughter of one of the women in the study. She wrote that her mom found the website an incredible lifeline for her because unfortunately, her mom had metastatic cancer. It was very advanced. When she participated in the study, she came to the workshop. She was mobile. She was able to get out and around.

As her health declined over that next six months, and we measured outcomes primarily at six months, her health declined over that six months. So, her daughter said that Project Connect was her lifeline to other people. She couldn’t get out and around, but that she could communicate through her website and others could communicate to her. She could tell selected people when she was up for a visit, and she could tell people when she wasn’t, so the daughter said, “Thank goodness for this.” To have that kind of meaningful impact on a woman’s life toward the end of her life and her daughter, that’s part of what keeps me going every day.

Chris Riback: I would imagine so.

Dr. Annette Stanton: Okay, so let’s talk about the broader scientific reaction. Well, I have to tell you that I didn’t get any negative reactions from the science community. That’s partly because, I think … I think there a couple reasons for that. One, I did use an experimental method. I randomly assigned women to either this particular condition or in this case, a no treatment control, a standard care control.

Now, that still has some limitations in methodology, but at the same time, the findings were so consistent from Project Connect Online that I didn’t have a lot of skepticism about that, about the findings. Now, you do have to continue to replicate these kinds of studies and to compare them to other kinds of interventions. So, I think that that’s really important to do regardless. We all would know that.

I think the second thing that probably helped is that I didn’t say that Project Connect Online does anything to cure cancer. We were interested in specific outcomes, depressive symptoms, loneliness, life appreciation, feeling confident in one’s ability to cope. I think having those specific outcomes and measuring them in validated, scientifically accepted ways made the results more convincing. I didn’t attempt to say, “This is the next cure for cancer,” because I don’t believe that.

That said, some of our writing studies … Now, I’m not talking about Project Connect Online, but a different type of writing study that I mentioned before, having women write about their deepest thoughts and feelings about their cancer experience versus the positive aspects of their cancer experience versus just the facts of their cancer experience, one of the outcomes we’ve used in that study, for example, is over the next few months, whether women have appointments with their oncologists that aren’t for standard scheduled reasons. So, that means that they’ve had some kind of problem so that they make an appointment with their oncologist because they’re worried about something, right? They have a symptom that they’re worried about.

What we found is that writing about one’s deepest thoughts and feelings compared to just writing about the facts of the cancer, the women who wrote about their deepest thoughts and feelings had fewer medical appointments for cancer-related problems with their oncologists over the next several months.

Again, that isn’t about curing cancer, but it is about the kinds of potential physical health benefits and the ability to do well both psychologically and potentially physically if you attend to some of the other aspects of survivorship.

Chris Riback:         If I could, with apologies, I know I’m supposed to be asking you about the application of your work to breast cancer, but it’s occurring to me and I imagine the folks listening, is what you’re describing able to be extrapolated? I don’t want to hold you to a proven scientific … You may not have researched this, so this may be asking you your hypothesis, can this be applied to other aspects of one’s life?

You study stress. You study the emotional responses to stress in emotional and actionable ways to mitigate stress and improve one’s quality of life, and you’ve just described how you apply that to situations around breast cancer. Just briefly, to go outside of breast cancer, can one extrapolate some of these lessons to other stressful times in one’s life, or is that dangerous to do because you haven’t studied that necessarily?

Dr. Annette Stanton: I haven’t studied that very much, although we do some basic writing experiments with more than breast cancer patients, but one of the reasons I started these writing studies was because I was really interested in the effects of emotional expression versus emotional suppressing, suppressing emotions, not expressing them.

I came upon a line of research. It was started by Dr. James Pennebaker, and he had demonstrated that writing, what he called expressive disclosure, expressive writing, in basic experiments with people going through stressors, and this could be undergraduate college students and then other samples, had these effects on both psychological and physical health.

In part, I started these experiments because I didn’t believe his findings. I was skeptical. How could this kind of experience, this kind of getting people to express deepest thoughts and feelings in an experimental setting, have both psychological and physical health benefits?

So, we started a line of studies and one of them, I was already working in cancer, and so my first one other than a young adult population was in women with breast cancer. I was really surprised to find that we found similar findings. So, actually, in the larger literature, these kinds of approaches have been used in scores of studies and reviews, systematic reviews, what’s called meta analysis, which is a way of aggregating a bunch of studies’ findings together quantitatively, do show benefits on both psychological and physical health parameters.

Now, those findings are consistent. They’re reliable, meaning consistent, and they do tend to hold up. It’s not a panacea. It doesn’t take away all problems. It’s not any kind of miracle, but it is one tool maybe in an armamentarium of resources that can be used to help people get through stressful experiences.

Chris Riback: Can we talk about you? You were born in France. You grew up in a small town, I understand in Kansas.

Dr. Annette Stanton: I did.

Chris Riback: I confess, I hear neither a French nor a small town Kansas accent, so I’m going to have to rely on the research that all of that was accurate.

Dr. Annette Stanton: It’s definitely not French. We were two when we moved back over. My dad was career military, and so it’s not French unfortunately. That’d be sort of fun, but this is my small town Kansas accent, maybe. Yep.

Chris Riback: Maybe. Okay, fine. I’m no linguist. But my sense was that you don’t hear about that background necessarily very often, and it struck me that perhaps a quasi-unique background must play a role in your unique take on stress and illness and recovery. Do you ever think about that? Is that accurate? What do you think about you translated into thinking about the world this way?

Dr. Annette Stanton: I know for sure one thing that did, and that was I did come from a town that had, when I was growing up, and I think still, because I’ve been back, has no stoplights. It is a truly small town. Part of what motivated me, I have to say, was growing up in a stoic Midwestern family, and we sort of didn’t talk about stressors very much. We didn’t talk about things that were hard. So, that’s sort of that quintessentially stoic Midwestern Kansas farm girl family.

Then, I have to say that my personal background is that I went to the University of Kansas, and then I did go on to graduate school and when I was studying for my PhD, my father got diagnosed with cancer. So, I both was in my family and watching my family go through this in our really stoic way, and at the same time, communicating in our own ways how important we were to each other.

At that same time, I was on my clinical internship at a big, big medical school, medical complex. I was beginning to watch people go through diagnoses of life-threatening things. I just became really fascinated in how some people become completely slumped by their disease, and in fact most people frankly do just fine. It’s not that it’s not hard, but most people recover well and do well in life, and so I became really fascinated. That sort of convergence of the personal and the professional, it started me on my career track of trying to figure out what helps and hinders people and then what we can do about it.

Chris Riback: Wow. I can imagine how influential that was. I guess there are many people who are benefiting today from the fact that you grew up in a very stoic Midwestern environment.

Dr. Annette Stanton: I hope so. I benefited from it.

Chris Riback: It sounds like you have. It sounds like you have. Just to close out, there’s all sorts of positive support obviously for the work that you do and you’re at UCLA and there’s incredible resource there. What role has BCRF played in your research?

Dr. Annette Stanton: I literally could not do my research without the support of BCRF. I’ve been here at UCLA for 15 years. Once I got supported by BCRF, I just can’t imagine being able to do … Well, no, I can’t imagine. It’s just simply true that I couldn’t do my research in the same way without the support of BCRF.

BCRF really allowed me to pursue these kind of unusual ideas. Project Connect Online came from a patient who was in my other research studies. It was fascinating and I wanted to try it out, and it’s really difficult to get support when you’re a little bit starting from ground up.

BCRF I think trusted the research that the researchers supported by BCRF do to trust me along with other vending agencies, but to trust me to do that kind of novel, “Let’s try this out and see where it goes, and then let’s develop it along the road into really a program of research that ultimately gets translated in the real world in the clinic.” BCRF enables that. I couldn’t do that kind of, especially that early phase research, without BCRF.

Chris Riback: Wow. Anyhow, that’s terrific that they do that and terrific that that’s enabled the work that you do. Thank you. Thank you, Dr. Stanton, for your time and obviously for your work.

Dr. Annette Stanton: My great pleasure. I’m so grateful to be able to do this work.

Chris Riback: [Narration] Hi. It’s Chris. I thought our conversation ended there, but I asked Dr. Stanton if there was anything else she wanted to discuss that we hadn’t gotten to. She reminded me that I was curious about her important endocrine therapy studies and strategies to help women stay with the therapy. Here’s what she said.

Dr. Annette Stanton: Well, first we needed to understand what was contributing to women not taking their endocrine therapy and what helped women take their endocrine therapy. By endocrine therapy, we’re talking about agents like [inaudible 00:40:07] and the aroma taste inhibitors that women often take often following their breast cancer treatments, surgery, chemotherapy, radiation, and those, and then continuing for years.

So, typically it’s a daily pill that women take for, the prescription used to be five years. Now it’s 10 years and sometimes longer, and it is a life-preserving treatment, so the importance of taking your endocrine therapy really can’t be underestimated.

So, we first tried to understand the factors that contributed to endocrine therapy non-adherence. That is women not taking their endocrine therapy as prescribed or what’s called non-persistence, women stopping their endocrine therapy.

We first did a study of more than 1000 women. It was a one time survey study, and we assessed a number of factors that we thought might correlate with, relate to women’s non-adherence, and this was self-reported non-adherence, which has some problems but does correspond at least to some extent with objective measures of adherence, and we were interested in those women who had stopped their endocrine therapy even though they had been prescribed to take it for a long time. So, we were interested in those factors.

In that first study of more than 1000 women, what we found was that a less trusting relationship with their oncologist, so a relationship with their oncologist that was not as trusting, not as positive as it could be, a lower perceived need for the endocrine need. So, they basically perhaps hadn’t been told or didn’t believe the research that shows that endocrine therapy is associated with better survival from breast cancer. More negative emotions about the endocrine therapy. Those kinds of factors were associated with more self-reported non-adherence.

Also, those women who had stopped their endocrine therapy also were more likely to report more depressive symptoms, and so they were more likely to be depressed than women who adhered to their therapy. They also reported more negative emotions related to their endocrine therapy, lower positive emotions.

The original idea in some of this research was that basically, it’s all side effects. Women don’t take their endocrine therapy because they have side effects from it and so stop taking it. We actually found that the factors I just discussed were more potent in their relationship with non-adherence, self-reported non-adherence, than were the side effects that we assessed.

So, that was a little surprising to us, and I’m not saying that side effects aren’t important. They really are, and there are several other studies that suggest that they are important, so side effects are important, but there are other factors that also can be actionable that we can intervene on that might help improve adherence.

Then, in another study funded by BCRF, this one, we followed women from the start of their prescription through several months. We actually had both self-reported adherence, and it was an objective indicator of adherence. Basically, it’s a little electronic cap that sits on your pill bottle and every time you open it, it’s assumed that you’re opening it to take a medication and so it records the date and time that you took it, and so you can measure daily adherence electronically.

There, we also found that depressive symptoms predicted lower adherence across the first month of being prescribed endocrine therapy. One of the factors that was important in predicting more depressive symptoms was lack of social support both by the oncologist and by women’s loved ones.

So, that kind of lack of support, depressive symptoms, and objective measures of adherence were our findings in another study. Now, we’re trying to translate those findings into action through beginning to test approaches to help women stay on their endocrine therapy, so we’re in the middle of that research.

Chris Riback: Thank you. I’m glad we got to cover that. That’s, as well, incredibly important stuff, so thank you.

Dr. Annette Stanton: Oh, sure.

Chris Riback: That was my conversation with Dr. Annette Stanton. My thanks to Dr. Stanton for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.