Radiation therapy has long been a mainstay of breast cancer treatment for many patients. Like other areas of cancer care, the goal is always to reduce risk as much as possible while still maintaining benefits. For patients undergoing radiation therapy, one key risk is unintended radiation exposure. In cases of breast cancer that occur in the left breast, for example, unintended radiation exposure to the heart can increase the risk of heart failure. So how could doctors limit this kind of damage?

Enter Dr. Rachel Jimenez and her research on proton beam radiation. Unlike traditional radiation, proton therapy radiation can target cancer cells specifically, sparing other healthy tissues from potential damage. Additionally, as part of her Conquer Cancer Foundation Advanced Clinical Research Award for Diversity and Inclusion, Dr. Jimenez and her colleagues are exploring whether proton beam radiation therapy could be delivered effectively in a shorter time span than traditional radiation, cutting down on the disruption to patients’ lives.

Dr. Jimenez is an assistant professor of radiation oncology at Harvard Medical School and the chair for quality and safety in the department of radiation oncology at Massachusetts General Hospital. Dr. Jimenez also serves on multiple national committees in oncology as well as various professional societies and patient advocacy organizations.

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

Dr. Rachel Jimenez: Thanks for having me.

Chris Riback: I thought we should start with your specialty: radiation oncology. Given the range of cancers, why did you choose to apply your specialty so significantly towards breast cancer? Why this discipline? Or by chance, do I have that wrong and you apply your time equally across all cancers?

Dr. Rachel Jimenez: You do have it right. So the majority of my time is spent caring for patients with breast cancer. And in the academic setting in which I practice that’s quite common. So academic physicians often will focus their practice on a specific type of cancer because it allows us to really delve deeply into the management of patients with that given cancer type. In my case, breast cancer. So we’re really thinking about how to care for those patients most carefully and are able to then lend our thoughts towards the creation of clinical trials and other types of research that we think are most likely to benefit those patients.

Chris Riback: And what drew you there?

Dr. Rachel Jimenez: As a trainee, as a resident, I really enjoyed caring for breast cancer patients. And while I enjoyed caring for many patients of many different types, I think the reason why I was drawn to breast cancer patients is because I feel like many of those patients are multi-hyphenate. They are mothers, they are wives, they are employees. They carry many, many different roles in their lives on top of managing their breast cancer and going through treatment. And I was really inspired by so many of the patients that I met, just seeing how many hats they wear despite the challenges. And it’s just a very inspiring group of patients to get to take care of.

Chris Riback: Which leads to my next question, which I wrote based on something I’ve read about you, but I feel maybe I chose slightly the wrong word. And my question is, what’s the role of compassion in what you do? And listening to you right now, maybe it’s not compassion, maybe it’s empathy, maybe it’s both. But in learning just a little bit about you, not a ton, it’s evident that that’s a key theme across who you are, how you engage with patients, how you think about your work. So tell me, if you would, how you think about compassion or empathy or any other word that you choose to throw in there?

Dr. Rachel Jimenez: Well, first of all, thank you. That’s very kind. I mean, I would like to think that all physicians go into medicine because they have an abiding empathy or compassion for the people that they care for. And I do think that it really is a privilege on our part to get to care for so many wonderful, impressive, steadfast, and dedicated patients. And I think that that’s the joy in what we get to do is to serve them in some small way on their journey to cure their cancer. So for me, I would like to think that that’s not a unique aspect of my practice, but I think it is the component of my practice that gives me the most satisfaction, which is really getting to know people as people—who they are, what they value, what’s important to them. And then be able to, again, in some small way care for them and to honor their values in the process.

Chris Riback: I love your use of the word dedicated, how dedicated the patients are. It’s such a multifaceted description and so accurate, and I haven’t heard it necessarily characterized that way, but it absolutely comes across in every conversation that I have with researchers, scientists, physicians, caregivers like you is the dedication. Because so many of the patients, yes, they are on a very, very challenging, to say the least, personal journey. And yet so many of them—and we’ll get to talk about this in a moment when we get into your clinical trials and your studies and your research—and I’ve heard it with other researchers, they are dedicated to the cause to other patients, to not just their journey so often, which has to be all-consuming, but also helping advance and discover and research for themselves but also for others.

That’s a really interesting and fantastic choice of words to describe their dedication, which it really is. It takes dedication to get through years of medical school and training, but it takes a different and really extreme type of dedication to be a patient. And that’s really thoughtful of you to recognize, of course.

Let’s move to the numbers. Approximately 60 percent, as I understand it, of breast cancer patients receive radiation therapy as part of their care. Why is that and how does that number compare historically? And I guess if I could pile on, in an age of increasing velocity of customized therapies and approaches to me as a lay person, an outsider, that 60 percent number feels high. So, talk to me about the 60 percent and how does it compare historically, please?

Dr. Rachel Jimenez: Sure. So the 60 percent may also be historical because we’re seeing so many advances in breast cancer therapy where we may be able to forego radiation, where patients don’t necessarily need to have radiation with a diagnosis of breast cancer. But to answer your question, historically, and I guess it depends on how far back we want to go, patients were treated quite radically even for very small early-stage breast cancers. And so many patients underwent mastectomy. And that mastectomy could be a fairly dramatic procedure with long-lasting morbidity for patients and cause a lot of side effects and really inhibit their quality of life.

And so there had been a number of clinical trials that explored the idea of instead of a radical mastectomy, doing a less aggressive procedure called the lumpectomy where we remove the cancer, but we preserve the breast of the breast tissue. And what we found was that adding radiation to the treatment, meaning delivering radiation to the intact breast after the patient had had the cancer removed, seemed to confer the same cure rates as doing a more radical mastectomy procedure.

So, when that data matured and we saw that the outcomes for those patients were just as good, the standard of care really began to limit the extent of surgery such that for early-stage breast cancer patients had a lumpectomy and radiation, and so they went hand in hand. That meant that many patients with early-stage breast cancer received radiotherapy. So, I think that’s where we’re getting that 60 percent number. And then there are other patients for whom the cancer may have left the breast but not traveled far away in the body, maybe into the lymph nodes underneath their arm, where they could still have curative surgery with a mastectomy and removal of some of those lymph nodes and might still benefit from radiation as a way to kill any small amounts of cancer that could be left behind even after a surgery like that.

So, the combination of both patients with early-stage breast cancer having a lumpectomy but preserving their breast and this other cohort of patients who may have still required a more aggressive surgery but could still benefit from radiation treatment afterwards gets us toward that 60 percent. Now, as I mentioned before, we’re starting to, I think, decrease that 60 percent number. There are patients who, as we learn more about breast cancer, have not very aggressive breast cancers. And so they may be adequately cured with surgery and some medication alone and they might not need to have radiation. And so now we’re seeing that older patients, patients with small cancers that are very favorable in their tumor biology, might be able to safely forego radiation treatment with still excellent cure rates.

Chris Riback: What is proton beam radiation?

Dr. Rachel Jimenez: Proton therapy is a type of radiotherapy. Typically, when we use radiation as a way to cure cancer, we’re using X-rays. And so those X-rays are the same X-rays that a patient might get when they go to the dentist and get an X-ray or when they have some other type of imaging if they break a bone. But we’re using the X-rays in a different manner. We’re using them at a higher energy as a way to damage the DNA of the cancer cell and prevent that cancer cell from growing.

With proton therapy, instead of using X-rays we’re actually accelerating subatomic particles called protons. And so those protons have a different physical property. The beam of the radiation behaves differently than X-rays do. And so the potential benefits of proton therapy is that we might be able to direct the radiation at the area that we think could be harboring cancer and that the radiation beam would stop after it treats that particular area, it doesn’t continue to travel through the rest of the body. This means that we’d be able to spare some normal tissue from getting exposed to radiation when we wouldn’t intend to give radiation to that area. But where X-ray therapy might still deliver X-rays, again, not intentionally, but because of the property of the X-ray that it may continue to travel through the body.

Chris Riback: And do I understand correctly, some of the tissue that people like you worry and have worried about with the X-ray form, let’s say, of radiation is particular to the heart? Is that correct?

Dr. Rachel Jimenez: That’s right. So for patients who have breast cancer, we’re always thinking about what are the parts of the body that are near the breast that might inadvertently get radiation that we don’t want to give radiation to? And so the heart is one of those.

The reason is because historically with radiation, we didn’t really have as many tools as we have available to us now. When we planned radiotherapy, it was pretty crude. So we would deliver the X-rays to the best of our ability using pretty limited anatomic knowledge of where things were in space. We could see the breast, but we really couldn’t see internally to understand where the heart was in relation to the breast. And in that era when we were delivering radiation in that manner, we saw that low doses of radiation to the heart did translate into a higher risk of heart disease for patients as they age. So we were curing breast cancer, but then we were finding that those patients were more susceptible to heart attacks and other things later. We were accomplishing the exact opposite thing of what we were trying to do, which is cure these patients and give them a great quality of life as they got older.

Now we have a lot more techniques that are available to us where we can visualize the internal parts of people’s bodies and see where their hearts and lungs are in relation to their breast. And we do that using CAT scans. And so most radiation planning these days uses a CAT scan so that we can actually see inside and try to avoid exposure of the heart and the lungs when we deliver the radiation. But there are some patients for whom even when we can see where everything is, there are some limitations to the technological delivery of the radiation that would still confer some radiation delivery to the heart and the lungs even when we didn’t want to, just because the techniques are limited to some degree. If the heart’s really close to the breast or to where the cancer is, it’s hard to avoid treating some of the heart with radiation.

So the potential benefits of proton therapy are that we might be able to better spare the heart, even in patients who have cancers where that is located very close to the heart. And so, I think that there’s a lot of interest and excitement about the ability to again, preserve the health of many of these patients who, aside from their cancer, are very healthy people that we’d like to see have great quality of life for many decades after we cure their cancer. And proton therapy may be a way to achieve that.

Chris Riback: There certainly is a lot of excitement around it. And some of that excitement is translated or has been translated into, I believe, funding or at least some type of support for a study that you and your team are undertaking. Tell me about the study around proton therapy. How will you do it? What will the research look like? What’s the current status?

Dr. Rachel Jimenez: Sure. I’ve been very fortunate that BCRF has funded the study that we’re looking at. My interests from a research perspective are always in trying to make treatments less burdensome and safer for patients. This particular study is really looking at both of those things together.

Just to provide a little bit of context, when patients receive radiation for breast cancer, often those patients that receive treatment need to have treatment daily Monday through Friday for a period of weeks. And again, historically it used to be that many patients required between five and seven weeks of daily radiation, which if you have a job and you have a family and you have other obligations can be quite burdensome. And radiation therapy is not something that we can just strap onto our back and bring to your door. So patients have to drive to a facility that has that capability, which means that many patients are driving quite a distance every day for multiple weeks to receive treatment.

So there has been a change over the last few decades to try to move towards shorter, more compressed treatment schedules for patients so that they don’t need to come in for such an extended period of time. That we could deliver radiation instead of over six or seven weeks that we could deliver that same radiation course over three to four weeks. And so we’ve seen that the treatment schedules have gotten shorter, which is much more convenient for patients. And so then the question becomes, how short can we go? How few treatments can we actually achieve safely?

So there has been a lot of interest in a one-week treatment schedule, and this has been explored in some large randomized clinical trials for early-stage breast cancer where they have found the same great local control rates, the same cure rates in these patients, and the same side effect rates in patients using a very compressed schedule over one week instead of these longer courses of treatment. So I think that is a big win for patients. And certainly if I were a patient and I had breast cancer, I’d like to think that I could get my cancer treated in one week and have minimal disruption to the rest of my life compared to having to commit to six or seven weeks.

And so in this particular study, what we’re doing is exploring this one-week regimen of treatment for patients who require breast radiotherapy, specifically those who require left-sided breast radiotherapy, where we’re worried about the heart. And we’re comparing proton therapy as we talked about and those potential benefits with regular radiation. We’re trying to determine if patients who receive proton therapy show less damage to the heart or less changes to the heart compared to those patients who receive regular radiation.

Chris Riback: And one, what’s the status of the study? I believe you might be in the stage where you’re securing patients, but maybe you’ve advanced beyond that. And two, for the older form of radiation, is the potential damage or when the damage does occur to the heart, is that evident immediately? Or when you’re doing this study, are you going to have to wait X years to see in column A, did the old form create damage and the new form did not?

Dr. Rachel Jimenez: Great question. So for most patients who have radiation, side effects do not appear right away. And so that’s been a real challenge for us because if radiation therapy is causing damage to the heart, but we don’t know it for 10 or 20 years, then it becomes very difficult to be proactive in caring for those patients and in telling patients very transparently when they get treatment what the real risks are to them. So we can look at a population of patients in a study and say, X number of patients have heart disease, but that doesn’t matter to the person in front of you. They want to know if that’s going to happen to them and what they need to do to take care of themselves.

So in this particular study, we’re utilizing an advanced cardiac imaging technique. We’re using a cardiac MRI. Looking at patient’s hearts with a cardiac MRI allows us to see if there are any subtle changes to the heart—things that we wouldn’t be able to pick up just by looking at someone or examining them in our office that would confer to us that this patient might have an increased risk later of a cardiac event.

And so using this kind of imaging gives us a tip-off that this is a patient that we should be thinking about more proactively and caring for more proactively from a cardiac perspective. And I’m excited about this because I think that oftentimes as radiation oncologists we sit on our hands and wait for side effects to happen. But what’s really compelling about being able to study patients in this manner is that we don’t have to wait, that we can actually communicate to patients that we don’t know for sure if you’re a patient who will have a cardiac event, but we can see on your imaging that you have some changes, and this makes us want to be more proactive about your survivorship care.

Chris Riback: Yes, I would assume that it’s fantastic for you in your role to know that, and it’s central to the patient and in their situation to know that. And so where are you in the study right now?

Dr. Rachel Jimenez: So we are actively accruing patients to this study. We’ve accrued about a quarter of the patients so far. It seems to be quite a popular study for reasons that I think we’ve spelled out, which is that patients are looking for ways to make treatment more convenient and safer for them. And so I’m excited to see how the rest of the accrual goes and to encourage our patients to think about participating if it’s something that has interest to them.

Chris Riback: How did you get into this? Let’s talk about you a little bit. I mean, going way back, where did you grow up? For you was it always science or were you this close to being an English professor?

Dr. Rachel Jimenez: Not super close to being an English professor. I grew up in Connecticut. My mom is a nurse, and I think the idea of taking care of patients was very present when I was a small kid. My mom was a pediatric nurse, and we used to spend time in the hospital with other kids who were hospitalized and didn’t have visitors. Sometimes she would bring kids to our home if they didn’t have family situations where people were visiting them. So from a young age, I really seemed to absorb from her the importance of caring for patients in a very personal way.

And while I did not know that I was going to be a doctor right away—it took me some time to figure that out—I think that I always was very interested in and engaged with people and what they valued and what was important to them. And I think cancer care has a very special way of providing that relationship between patient and physician. What patients go through is such a life-changing event. And so again, it’s such a privilege as a physician who’s caring for them in that context to be on that journey with them, to serve them in that way. And so I think cancer care really stood out for me pretty quickly when I started medical school. And I still believe that it is the best specialty and the one that I feel just truly privileged to get to be a part of.

Chris Riback: Well, obviously the compassion gene does not fall far from the tree. Is your mother still alive?

Dr. Rachel Jimenez: She is. Yep. She’s retired now.

Chris Riback: She’s retired now. Well, we need her back. What does she say about what you do?

Dr. Rachel Jimenez: Obviously, I think she’s proud of me. She’s proud of all her kids. And I think that it probably makes her feel some level of satisfaction to see that the field that she was so dedicated to for so long is something that continues in the next generation. I think that my family has had their own experiences with cancer over the years. My dad is a cancer survivor. Many of my family members are cancer survivors. And so I think that that adds an extra connection to cancer care, even though that was not her focus when she was in medicine.

Chris Riback: There’s one other area, if I’ve read about you correctly that I believe another aspect of cancer care—indeed medical care—that I believe is of interest to you, which is cultural diversity. Why are you focused there? What does it mean to you, and what actions or behaviors does it inspire?

Dr. Rachel Jimenez: I think from a cultural diversity standpoint, I am the product of cultural diversity. I come from a family that has roots and backgrounds in many places. And so I think that from a young age I knew or was aware of ways in which I was a bit different from other people in my community just based on my cultural, ethnic, and religious background. Coming from a family that is so rich in diversity, I think that I see not only myself reflected in conversations about diversity but also just recognize the value of different perspectives, different walks of life, different life exposures, and how important it is to honor those things and promote those things in medicine.

So my patient population tends to be relatively diverse in Boston, and I’m very gratified by that. I think it makes me very happy to see people from all different backgrounds and walks of life come through the door and make sure that when we are caring for them, we’re caring for them as well as we possibly can regardless of their circumstances in life. And I know that there’s been a lot of attention paid in medicine to reducing those disparities across the board, and I feel very passionately about doing my part to do the same.

Chris Riback: You certainly are doing that, it’s evident. To close out, I know you touched on it briefly before, but what role has BCRF played in your research?

Dr. Rachel Jimenez: I am just incredibly, incredibly grateful to BCRF because the research that we’ve talked about simply would not have been possible without them. I think one of the really special parts of BCRF is that they fund research that might not be readily fundable through other mechanisms simply because of the study design or the type of question that not all study sponsors would be supportive of that kind of work. So I’m just incredibly gratified that BCRF saw the value of this research and was willing to support it because it makes all of the difference, not just for me, but potentially for the advances that we can offer patients.

Chris Riback: Yes, I’m certain that it does. And Dr. Jimenez, thank you. Thank you for your time, of course. Thank you for the work that you do, the compassion, the empathy, but also the imagination and the care that it’s so evident that you give. Thank you.

Dr. Rachel Jimenez: Thanks so much, Chris. I appreciate it.

When we think of treating or preventing illness, the role diet plays in keeping your immune system healthy often comes to mind. But how many of us would think of fiber as essential to healthy immune system function?

That’s where Dr. Laura Esserman and her research on immune-driven breast cancers come into play. She’s focused on examining the effects of a fiber-rich diet on the gut microbiome and biomarkers of immunity in women with newly diagnosed breast cancer. Her prior research looked at how immune cells in tumors influence tumor response to immune drugs, and she believes the gut microbiome plays a key role in this complex system. Her work serves as a reminder that, much like the gut microbiome–the plethora of bacteria in our digestive system–patients should also be treated with personalized care.

A BCRF investigator since 1998, Dr. Esserman is an internationally recognized breast surgeon, breast oncology specialist, and personalized medicine visionary. She has led the I-SPY series of trials since 2002 in collaboration from the NCI, FDA, and more than 20 cancer research centers and major pharma and biotech companies. The trial approach has become an international model from translational research because of its design, which shaves several years and tens of millions of dollars off of the drug development process. Dr. Esserman was included as one of TIME Magazine’s 100 Most Influential People of 2016 and received the 2018 Giant of Cancer Care in Cancer Diagnostics award. She has published over 300 articles in peer-reviewed journals.

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

Dr. Laura Esserman: Oh, thank you for having me.

Chris Riback: So I think you might be the exact right person to ask if this life statement that we’ve all heard is actually factual. Is it true that we are what we eat?

Dr. Laura Esserman: Well, I think we are not exactly what we eat, but we create an entire environment based on what we eat. I think what’s so fascinating about our bodies is that we did not realize until maybe 10 or 15 years ago that, especially our whole notions of what is sterile and how to keep things clean or what are you eating? Well, it turns out that what you eat influences the immense number of colonies in the ecosystem in your gut, and your gut is probably the second most important immunological organ in the body. So what you eat is broken down by various bacteria and enzymes in your gut. So it’s a cascade of everyone is what they eat. So you are what you eat, the first bacteria that break it down eat that, and then another colony grows to eat that, etc. So you start the chain by what you eat, and that chain and those bacteria that grow there actually do truly influence your immune system. We don’t understand it anywhere near as well as we should, but I think one thing is clear is that fiber is the key—not probiotics, but eating fiber. I think avoiding antibiotics when you can and eating fiber sets up that ecosystem, or that chain of bacteria that are healthier for you in so many ways, and I think really protect your immune system.

Chris Riback: So tell me, please, why you say that, and maybe what are fibers, just to oversimplify, what are fibers and what are probiotics?

Dr. Laura Esserman: So fiber is that stuff in food, like in spaghetti squash, or avocado has a lot of fiber, raspberries have a lot of fiber. Fortunately, popcorn has a lot of fiber. You can look up the amount of fiber that people get and around the world, people have different amounts of fiber. In the US, 90 percent of people get less than 20 grams a day of fiber in their diet, where probably we should try and aim for 30 to 40 grams of fiber in our diet. One of the colleagues I’ve been working with, and in fact, one of my BCRF projects this year, is to try and figure out how much time it would take to change the microbiome in the gut before surgery.

Can we change it with two weeks of a high-fiber diet? That fiber, again, starts that chain of bacteria that give you the kinds of ecosystem that is actually really healthy for you and stimulates the immune system and the gut and is very protective. A group at MD Anderson has shown this, that in melanoma, for sure, they tested fiber against the probiotics. Probiotics are the things you can buy in the drugstore, that’s in the yogurt or the various things you can reconstitute all the good bacteria in your gut, that’s how they’re advertised. We have no idea what’s really in them. And it turns out they’re not helpful, in fact they’re harmful. You have to be suspicious of that kind of thing.

And as it turns out, in every study where we’ve tried to study vitamins and food, the most important way to get the right kind of vitamins is through food. People say eat the rainbow—that’s try and have a rich plant-based diet. Even if you do eat meat, or you do eat other things, just making sure that you have enough fiber is so important. And I can’t tell you that I know this for sure, but I think that one of the reasons why we have had such a hard time exactly figuring out what the food relationship is to cancer is that there’s an intermediary, and that intermediary are all these bacteria, the ecosystem of bacteria and the gut. I’m collaborating with a professor at UC Irvine who I met at the AACR Rally for Medical Research in Washington. We were in the same group.

Chris Riback: Of course, why wouldn’t two California researchers find out about each other in Washington D.C.? Makes perfect sense.

Dr. Laura Esserman: She does the coolest thing. She teaches this class, this undergraduate class. They learn how to sequence their stool so they can figure out what’s in there, and so they do their own sequencing. And then she doesn’t make them stop eating pizza and the various things they would do as college students, but then she gives them this fiber-rich diet. So you can order these things from, so there’s companies like Thistle and others that will send you these high-fiber diets, and in two weeks their microbiome changes, and they re-sequenced it again. So they learn how to sequence, they learn what the science is, and they get to do the experiment on themselves. I think it’s super cool.

But I said, okay, two weeks might be enough. Just think about it, we give everybody two grams of Capsol at their operation. What are we sterilizing? It’s just so interesting that so many things that we do come from an era where we knew so much less. It’s often we’re stuck applying old principles to new data, when in fact we really have to throw some of that stuff out because our notions often are wrong about what we knew before. We started screening before we knew that breast cancer was many diseases, so it can’t make any sense to screen everybody the same. Everybody has different risk.

It’s hard for us to let go of what we knew from 40 years ago, but I don’t think it should be that hard to let go of it. And the same thing about ductal carcinoma in situ, we always thought, “Oh, it can’t be reversed, this is what you have to do, here are the principles.” But in fact there’s new data to suggest we should be doing things quite differently. How do you let go of old things when you have new information?

Chris Riback: That is a challenge for cancer research. That’s a pretty broad challenge I certainly could apply in many aspects of my life. You’re suggesting potentially, hey, could we assign/suggest a fiber-rich diet two weeks before, I think you said before surgery, to try to alter the gut microbiome situation? And you had said previous to that, I think, that the gut is the second most important immune organ outside the lymph in the body. So I’m hearing that and I’m thinking, well, wait a minute, is this preventative? Should I be going highest fiber possible yesterday? Yes, is the answer?

Dr. Laura Esserman: Yes. I think absolutely. It’s interesting just trying to look around the world and what people eat, and we used to think it was flaxseed or some of these other things, but I think it’s probably related to fiber. And there’s enough data to say that that’s a healthy thing to do. I’m sure everyone can find things in the list of high-fiber foods that they like, whether it’s beans or lentils or chia seeds for their yogurt or…

Chris Riback: Or raspberries.

Dr. Laura Esserman: Raspberries. I ate a box of raspberries, that is eight grams of fiber.

Chris Riback: Outstanding.

Dr. Laura Esserman: So there you go. So I’m a quarter of the way there, almost.

Chris Riback: I was just going to say, I was doing the math, you’re a quarter of the way to 30, for sure.

Dr. Laura Esserman: And then you find the things that you like, find fun recipes. This is one of these things where this may not be the panacea, but it absolutely can help you, and it’s good for you. They have to drink a lot of water if you eat a lot of fiber, because that’s important too. And the other thing that I like about it is it’s not expensive. Beans are probably one of the cheapest things that you can buy and make and learn how to make well, same thing with lentils. And it’s something that is, from an equity standpoint, it’s something that everybody can do and everybody can afford.

Chris Riback: I have had the privilege of talking to BCRF researchers like you—and BCRF-connected researchers like you—and many of these discussions have been with researcher scientists around the world and exactly what you just described. There are unique, regional, local challenges. Many of them around information, obviously access to care, but a lot around preventative measures. And for you to identify something as simple as increased fiber through beans, or lentils, very accessible. That’s really, really powerful.

Dr. Laura Esserman: You can do everything right and still get cancer, it’s not like a panacea. It’s always important to say these are things that you can do to help yourself, and it’s good for your health no matter what. It’s also good for reducing heart disease and everything else, but it doesn’t completely protect you from any of these things. And there are other factors, whether you’re inheriting a gene, or other things that can be the triggers for cancer that you can’t control. And it’s always important, I think, for listeners to understand there are things you can do to be a better driver, for example, these are those kinds of things, but it doesn’t protect you from the drunk driver that crosses the median strip and hits you broadside, that kind of thing.

Chris Riback: Thank you. Yes, thank you for emphasizing that. Short of choosing different parents, which of course none of us would want to do, but we have to-

Dr. Laura Esserman: Can’t do it. It’s a little late, right?

Chris Riback: It’s a little late for that. We have the genes that we’re given. Tell me about your current research. Which of the aspects that you have been talking about right now are you most active in? I’ve read about a program of yours where participants will receive 10 meals per week and recipes and it’s related to fiber. Is that your most current research? Is that the one we should be talking about? What’s the status?

Dr. Laura Esserman: So that’s one of them. I’m also trying to figure out how feasible is it to try and add in a fiber regimen to one of the neoadjuvant therapies. So this is in preparation. So there are three big trials, sort of four trials, that I’m running. And actually, BCRF has had a hand in all of them, as it turns out.

Chris Riback: Wow, that’s fantastic.

Dr. Laura Esserman: So always when I’m starting things up, BCRF has really made it possible for me to get over the hump of where I’m starting to get it rolling on its own. So the I-SPY trial is one of the longest-running trials that I’ve had, and this is taking people at a higher risk, early-stage cancer, stage II and III cancers, and we initially had it mostly for fast-growing tumors. And now we have an endocrine arm that we’re trying to figure out how to optimize endocrine therapy. Again, tailoring treatment to biology and giving the treatments upfront so that we can really understand how they work. There are some cancers that are where immune manipulation is really important, these are immune-driven cancers. These are where it may be super important to complement whatever treatment you’re giving with a diet that helps you optimize that immune response.

That’s what I’m trying to figure out. How feasible is it? How would we do that? There’s some data in melanoma to suggest it can make a big difference. And we actually, in I-SPY, saw one of our agents that was given orally interfered with the PD-1 inhibitors and you’re like, “Oh my God. This is the smoking gun. We have to pay attention to this. These are things that we weren’t paying attention to, and so how would you do that and how would you make that feasible?” And that’s one of the things that’s so amazing about BCRF is they’re like, “Oh, we can make what can seem like a crazy idea not so crazy.” And then if it works, now you’ve got the data to move it forward.

Now what I’m trying to, okay, well what if we thought it’s absolutely essential to have this high-fiber diet? Okay, how would I actually make that practical? How would I do that and how would I do it in a way that’s consistent, that I can put it into a trial, where people wouldn’t melt down saying, “Well, you can’t do that,” so where you’re doing it very consistently? We are actually, in I-SPY, testing the microbiome of patients before and after. We’re starting, we have a pilot for that also. And so we’re trying to understand, how big is the problem? How big is the variation? It’s a very complicated system.

But I-SPY in particular as a bigger entity, what we’re trying to do is start with novel agents. Now there’s so many exciting antibody-drug conjugates, bispecific antibodies, all these things, we always test them in the metastatic setting first, but I don’t know that’s where they have their best impact. Why not start them first? And if you get a complete response, if the tumor goes away, then you can stop. And if it doesn’t go away, then you go on to the best treatment for your particular subtype. And over the years, BCRF has helped us figure out, Dr. van ’t Veer and myself, what are the different subtypes? How can we re-understand or re-imagine the subtypes? So that’s a super exciting trial and that’s open at about 45 sites around the country now.

And then, based on this also, the other thing that’s so interesting is that most of the people in the I-SPY trial do not have screen-detected cancers. And so what do I mean by that? They’re either too young, they’re in their thirties because the average age for these bad cancers is 46, so a lot of people are young, so they’re out of screening age. And some of the cancers grow so fast that they can grow between screens. And some people aren’t screening. So are we doing as good a job as we can with screening? Are we identifying the people who are at risk for fast-growing versus slow-growing tumors? Are we thinking about it? Are we getting ourselves on a path to continuously learn and improve? We aren’t. So I started this, initially funded by PCORI, but when we needed more funding, BCRF actually supported us, they’re supporting us in this transition until we wait for our program project to get funded, which I’m always assuming we’re going to get funding.

Chris Riback: That’s a good attitude to have.

Dr. Laura Esserman: It’s always assumed, to live the expected life. It doesn’t always work. But the idea is to screen people according to what they’re at risk for. If you’re at risk for a fast-growing tumor, screening every two years isn’t going to work. Probably screening every one year isn’t going to work, if you really have high risk. We know that from the BRCA1 cases. The other thing that we’ve learned from doing this population-based genetic screening, 60 percent of the people who have a mutation that increases your risk for cancer do not have a first-degree family relative with cancer.

So family history is usually the way we decide who should get genetic testing. I reject that. This is a low-hanging fruit. Find the people at the highest risk. And so we are now lowering the screening age to 30. Just get that genetic risk and then you can find out who’s got the mutations, and a third of people who have these mutations get cancers in their thirties, or more. So we’re missing that whole thing. So again, trying to change the screening paradigm, and it can be actually much more cost-effective to do more for the people at very high risk and then less for the people who don’t need it, because then there’s a lot of harms that can be done. And then those harms include DCIS. This is a really tricky thing. It’s stage zero, or in situ. I don’t think we should call it cancer because that frightens people, and that’s why a quarter of people wind up getting bilateral mastectomy when they have DCIS. For some people that might be reasonable, but for most people that’s way overkill.

And I think we’ve always assumed that this was irreversible and that you’re on a path to getting cancer. But we have shown that a number of these, especially the hormone-driven cancers, will go away, or there’s not a focal or surgical thing. It’s just a risk factor. So I think about DCIS as prevention. And so you can see how this whole ecosystem, the big trial, leads you to rethink screening, leads you to think about, okay, what are the bad things that come from screening, is all these cases of DCIS that you find. And for years I’ve been working, that BCRF funded me to really think about, there’s about 20 percent of DCIS that are high risk, that are hormone negative or immune-driven, and they really do have a focal lesion. Sometimes they have these big lesions, and how do you get a five-centimeter or eight-centimeter mass that’s DCIS?

Maybe those aren’t the worst DCIS, maybe they’re the best, because somehow you’re keeping them from being an invasive cancer. And it turns out it probably is the immune system that’s helping. And what’s cool about that is that we have figured out immunologically how to stimulate it in just these last few years. This, again, has been a long-standing BCRF investment, to stimulate the immune system of these high-risk DCIS, and half of them, we’ve made them disappear in a month or two. And no one would ever have thought that was possible. Everyone says all those people have to go to the RNI [a form of radiotherapy], so I think it’s like being observant and saying, “What doesn’t make sense here?” How do you apply the principles we know today, not the principles we knew before? Because you have all this new information and you’re applying old standards.

And the thing that’s so cool about BCRF is it allows you to explore—and not everything turns out the way you want, but if you keep at it—it’s that consistent ability to follow new leads and say, “Oh no, this is possible,” that really changes the whole paradigm. I’m just launching a national trial and active surveillance for DCIS, and I’m expanding my vaccine trial, and if that works, hopefully we’ll get to move that program forward. We’ll see.

Chris Riback: What is it about you, do you believe, that allows you to recognize or investigate or be curious about such a wide web of instances, or points on the spectrum, of cancer care? What is it about you that has you thinking in that way when perhaps other people don’t? And it struck me that you might’ve just answered it. Is your superpower being observant?

Dr. Laura Esserman: Maybe. Maybe so. But I think also that I think to question. My superpower is to question constantly, and to ask, Can we do better? And I can look around. And I think my superpower is also to say, “Are we doing all we can for women who are either at risk for or who have breast cancer?” And the answer is no. Our treatments today are not so great. I have yet to have someone say to me, “Oh, wow, that sounds fantastic. I love that. I want to do that.” When they say that, okay, then my job is done. I have the ability to be honest about how well we’re doing. And I don’t look at it as a feeling, I look at it as an opportunity, an exciting opportunity to rethink how we should do things, constantly.

In college, I was a history of science major. And I think you get that really big perspective, which I think has been very influential for me, and I’ve had a lot of training in policy and in basic science, and that’s allowed me to be it. And then I have training in business management, I went to business school, so I’m a multidisciplinary person in my training. And so it’s allowed me to be a system integrator. And if you look back at the history of science, there’s so many things that we used to do that are ridiculous. Look, the guy who invented pithing, the frontal lobotomy, got a Nobel Prize. But you often admire things that are out of fashion, and it’s about what captures people’s imagination.

So I think having that bigger picture, and we used to say that old theories don’t die, the people that espouse them do, and so you like to aspire to not be that, and not be stuck in your ways. And I used to get in trouble when I was an intern in surgery, and I was always going, like, “Well, why are we doing that? Why are we keeping someone in an NPO [nothing by mouth]? Why can’t they have clear liquids when their stomach’s making a gallon or a liter of fluid a day? What’s the problem here?”

Chris Riback: You were history of science, so that’s a noble career and a profession to understand and write about and think about the history of science. Were you always going to go into science and that was just your path to get into it? Or did something happen and you transitioned from thinking to acting?

Dr. Laura Esserman: Well, I was always interested in science. And I had been working in a basic science lab even when I was in high school, all through high school. So always very interested in science and thought about being a basic scientist. But I love people and I love their stories. I find, for me, this compliment of clinical medicine and research, you can’t always change biology, but you can always make the transition and everybody’s journey better by caring a lot, and that’s the art of medicine, and just being there for somebody. But when you’re frustrated about what’s not working, that’s what your research is for. And I am interested in a lot of things that I think require bigger scale, that can’t be done with just one person. The I-SPY trial requires this huge organization that you’re running the experiment in a big way.

But I love taking what I hear and translating that into better trials, more patient-centered, more patient-focused. Where are the problems? Where are the levers? How do we use imaging as a catalyst to change? Because it’s like the difference—I’ve used MRI imaging, I was very lucky when I first came to UCSF I met Nola Hilton, who was writing the sequences for what became breast MRI She was actually getting her PhD at Stanford, but she came up to UCSF because there was no MRI machine down there, and it was up here. And she came to me and said, “How would you like to use this?” And I said, “Oh, I want to look at women who have stage II and III breast cancer and see if they all look the same.”

And at the time, we were treating every woman the same. And I’m looking, I’m like, “Wow, all these cancers look completely different.” I’m like, “Okay, well, let’s treat them first and see if they respond the same.” And guess what? They don’t. And so that gives you that opportunity that’s like, Why are you taking out the biomarker? I’m impatient, and I always, I know my father’s favorite sayings, but I always had in my office is the person who says it can’t be done will soon be passed by the person doing it.

Chris Riback: Great phrase.

Dr. Laura Esserman: I love that. And I am like, “Well, why can’t we do it this way?” And then you start talking to people, and Dr. Larry Norton actually helped me get it set up, and the corporate groups, when he was in charge there, but then they didn’t want to go at the pace I wanted to go and I was frustrated by how slow things were. I’ve studied a lot of other industries, that’s your history of science, and that’s what I took out of business school was also that medicine is a business like others, and you can either learn from other industries or not, and who’s it for? Your patients don’t have 10 years for you to get your act together. They need something faster.

There has to be an engine to drive change. And I was frustrated by the way trials were run. I was frustrated by every time you want to do a new idea, you have to start a new trial. I thought that was so inefficient and wasteful and I’m like, “Okay, there’s a better way to do that.”

So that’s how we started the platform trials and now that’s the way I do everything. And we have a not-for-profit, Quantum Leap Healthcare Collaborative, that is really working on fine-tuning the engine so we can do things fast, we can get things through a central IRB [investigational review board] in three weeks. You don’t want your time wasted over things that are immaterial. And people say, “Well, you can’t do that.” Well, that’s an invitation for me to do it. I like a puzzle. And I’m like, “Okay, I don’t accept that. That’s just a waste of everybody’s time.” It’s like I want to change the way we think about new drugs, which is if you take two drugs that are similar, but one’s less toxic, it doesn’t really matter, they have to do what they call a non-inferiority trial. Well, why is that? If it’s less toxic, why isn’t that superior? So now that means you have to come up with a new end point, which is efficacy and toxicity. And people say, “Well, we don’t do that.” I’m like, “Well, so?”

Chris Riback: Yes.

Dr. Laura Esserman: But it’s not like it’s easy, and it’s not like you have to gaze and say, “Oh yes, great, let’s do it.” They’re skeptical. But then the onus is on you to model it and figure it out and drive all these things. And it’s about assembling all bright young people to keep working on it and I want people to be hungry to move things forward and not satisfied with the pace of change. One of my colleagues, David Dilts, used to say, “People say, well, we have to be careful because we’re in medicine because people can die,” and he said, “Well, guess what? When planes fly, if things go wrong, planes fall out of the sky and people die. You aren’t the only industry where people’s lives are on the lines. Car industry, everything.” So it’s like you need to get out of this mindset that you can’t change. And that’s what research is all about, finding new ways. But then also, there’s this big gap between the ideas that you’re working on and how you get them to practice, and I see it as all one big continuum.

Chris Riback: It is evident that you do, and it’s also evident that you channeled that mantra of your father’s, and I am certain that the people who say it cannot be done are in your rearview mirror, you’ve passed them a number of times. Your patients don’t have 10 years to wait. You’re clearly motivated by speed.

Dr. Laura Esserman: I’ll tell you a very cool BCRF story.

Chris Riback: Yes, please.

Dr. Laura Esserman: Not this year, but last year, Jenny Chang came to me and said that she had this nitric oxide synthase inhibitor. And she said, “Oh, Lisa Carey told me to come and talk to you about it, that maybe you could put it in I-SPY,” and it was for triple-negative patients, that particular type of patient that didn’t respond. And I said, “Oh, we have the subtype,” and I said, “Oh, we’ll do that.” And I said, “Just get it back and we’ll get someone to start a company here, and I know lots of people in the industry anyway.” So that’s all happening and we’re going to put it into I-SPY.

The great thing was that I had a patient who, at UCSF, in I-SPY, had gotten one of the novel agents, one of the TROP-2 antibody drug conjugates. That didn’t work. Then pembro taxol carbo. That didn’t work. And then AC, it worked a little bit, but then it stopped working. And she had these big nodes in this, but she was forty-something, and I was just like, “Okay, I know the drug. We should really try and get that drug.” And we were in the transition and I couldn’t, we were trying to find a way to get it out of Houston Methodist, where Jenny Chang is, because it wasn’t in the company yet, and trying to get it from UCSF but couldn’t because they weren’t a pharmacy recognized by Houston Methodist. And I got compassionate use from the FDA to try it, and I finally, finally found a compounding pharmacy, our pharmacist here found it, it was everyone working on it. We were just about to give up and they were able to do it, and I gave it to her, and her tumor melted away. She had just a little bit left. That’s so cool.

Chris Riback: It’s unbelievable.

Dr. Laura Esserman: You hear something, you know it, you figure it out, you put it in, and it was because we were at the BCRF meeting that all of this is happening. You really live for those moments where “I can actually make a difference here.”

Chris Riback: Dr. Esserman, thank you. Thank you for your time. Thank you for the way that you think. It’s evident in talking to you that you’re the manifestation of that old Apple ad, think different. And thank you for the work that you do every day.

Dr. Laura Esserman: Well, thank you. And I think people think I’m unrealistic, but I think you have to be unrealistic. You have to aspire. But a man’s reach should exceed his grasp, or what’s the heaven for? Whatever that poem my mother used to read to me. So it’s like you aspire to be better, aspire to bigger, believe that it can be done, help lead people to that, and then it will get done.

There are some technologies that enhance human efforts and abilities and other technologies that make such a drastic impact, they revolutionize protocol and entire ways of thinking. AI in the healthcare field is one such technology. Scientists—including BCRF investigators—are working on ways to harness AI to improve how medical professionals interpret mammograms, and finesse and better personalize existing risk prediction models, and tackle disparities in screening and risk assessment.

That’s what Dr. Regina Barzilay is working to uncover. A BCRF investigator since 2022, she is a School of Engineering Distinguished Professor for AI and Health in the Department of Electrical Engineering and Computer Science and a member of the Computer Science and Artificial Intelligence Laboratory at MIT. She has received numerous fellowships, including a MacArthur “genius grant,” was awarded the first Association of the Advancement of Artificial Intelligence Squirrel AI Award for Artificial Intelligence for the Benefit of Humanity, and, in 2022, was elected to the American Academy of Arts and Sciences.

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Read the transcript below: 

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

Dr. Regina Barzilay: My pleasure.

Chris Riback: I just want to make sure that I’ve dialed into the right podcast recording. You’re an MIT School of Engineering Distinguished Professor for AI and Health in the Department of Electrical Engineering and Computer Science. We’re here to discuss breast cancer, correct? I didn’t dial into the wrong Zoom recording, correct?

Dr. Regina Barzilay: No, but you missed my other important title at MIT. I’m also AI lead for Jameel Clinic, which is a Center for Machine Learning and Health at MIT.

Chris Riback: Yes, it is a fascinating mix and intersection of skills and interests. I must confess that of all of your incredible fun facts, MacArthur Fellowship, the first recipient of the million dollar award, from the Association of the Advancement of Artificial Intelligence, I think the one that I found most amazing was that IEEE Intelligent systems named you to their AI “10 to Watch” list in 2006. I mean, most of us had no idea there was such a thing as AI back then and you were top 10. You’ve been on the cutting edge all your life, haven’t you?

Dr. Regina Barzilay: So it’s actually really funny when you’re talking about AI that at those times in 2006 it was not very popular term because people kind of thought about AI as all technologies, it didn’t work, so the list was not maybe the coolest list one can be in. So I was of course very flattered to be on the list, but for general audience, AI didn’t really mean much and it’s really kind of fascinating to see that previously I would say I work in this area and people say, “What exactly do you do?” Right now, I don’t even need to explain because everybody knows. So this was a big change throughout my career.

Chris Riback: ChatGPT is the best thing that’s ever happened to you?

Dr. Regina Barzilay: So I actually don’t use ChatGPT, but it’s really exciting to see how everybody else is using ChatGPT and how people are excited to see and it’s really spectacular to see this amazing progress that happened because when we are looking back at history with the kind of major technological breakthrough you can imagine, people always give the analogy of AI and electricity, but it’s true that if you’re thinking in 19th century when people didn’t have central electricity, when factories were powered by steam engines and other things, so how there was a translation that happened that slowly changed our lives. So it’s really interesting to be able to observe it through kind of my lifetime that from systems that could barely do anything. When I took my first class in processing, I didn’t even see any systems that can do anything productive to observing machine translation. This part was really super amazing to me how machines can really produce such beautiful translations, how the transcription of the speech improved over time. So I still remember those days when it was totally unusable technology. So it’s amazing to see it.

Chris Riback: Yes. And it’s got to be very reassuring to know that the rest of the world has started to come along to where you’ve been all the time where one has been, yes, I guess it must give a sense if one has an interest that has for so long, probably at dinner parties or a cocktail parties, although you probably hang out with much more interesting people than I do, but go and say, “Wait, wait, wait, what do you do? What is that?” And now the rest of us have not caught up to you by any stretch, but we’re at least in the same time zone as you are. So that’s got to be somewhat rewarding. So the connection between AI and breast cancer screening, what is it? And as I understand from reading about you, this work evolved from your own personal experience, didn’t it?

Dr. Regina Barzilay: Yes. So one of the areas where we actually don’t see AI at all when we experience it as a patient is a healthcare. I was just looking at Boston Globe, I live here, so in Boston Globe and there was this article about 13 users of AI by Boston citizens. People were saying different things. Somebody was using ChatGPT to write class descriptions, somebody was using it for planning meals. It was really stunning to see that nobody ever used it in any way related to healthcare. And it’s a very representative. There are lots of different measurements which are much more systematic than the story in Boston Globe that shows that there is truly no AI in healthcare. But if you’re thinking what AI is designed to do, is actually to do predictions and to do prediction about something where we have uncertainty because as humans it’s very hard for us to take data which comes from many different sources, put it together and kind of provide probability distribution over the outcomes.

This is not how our mind works. And also even if you’re very experienced doctor or expert, maybe you’ve seen in your life 50,000 patients. It’s a lot, maybe 100,000 patients, but you can send millions of patients, tens of millions of patients to the machine. And machine has this unique capacity to combine the data and to make these predictions. That’s how it’s optimized. And in terms of breast cancer, the specific area where I started, I started in initial language processing. That’s what I got my tenure and got all the many of their awards when I was younger faculty is work on the processing and where machine learning was always a part of how these tools are developed, ChatGPT-like tools.

In 2014, I was diagnosed with breast cancer. And this stunning thing was that there was really no AI. There is still no AI actually when you go to be treated, but there was none. And I wanted to see when I came out of my own breast cancer, I wanted to do something because I felt it’s really unfair to women that the technology in 2014 or ’15 was still not a year of AI for the crowds. But still this technology is not really is part of cancer care. And among many different ideas that I had, some of them were really stupid. But one of the ideas that I had was really to understand: What is your risk? Because I could never perceive myself being high-risk. Nobody in my family had breast cancer. I was athletic, relatively speaking. I was trying to eat well. I never drank or smoked. So based on the traditional risk factors I was not it. So, I just always brushed it because I don’t have family history or other factors, so why would I be worried?

And the question that I wanted to see is how you can predict based on the first mammogram that a woman takes or any subsequent mammogram, how likely is it she’s going to develop breast cancer? And this is a question in which to some degree clinicians are trying to answer without AI, and this is something which is called density, which shows you how much white on the mammogram you have. And every woman who does a mammogram in this country in the United States would get a letter that if she has dense breast that would tell her that she’s in increased risk of breast cancer and that her cancer may be missed. This is actually a new federal regulation. But if we are looking at this measurement, it’s a very faulty measurement because above 40 percent of women have dense breasts. So clearly not 40 percent of women likely get breast cancer or not even half of that.

So the question that we ask: Can you in a more accurate way to translate the pattern of a woman that we can see that she doesn’t have breast cancer? Can we take whatever is there and predict whether she’s going to develop breast cancer in the future? And that’s what we worked on using the power of machine learning to teach the machine to take the images of patients which look to us and look to the doctor cancer free and kind of assess what will be their trajectory in the next few years in terms of breast cancer.

Chris Riback: So describe for me if you would please, how does it work? What is MIRAI, M-I-R-A-I? I read a wonderful quote from you that with AI and the work that you’re doing and with MIRAI, we’re not just looking for the cancer, we’re looking at the soil that allows the seed of cancer to grow. So take me through the detail. How does it work?

Dr. Regina Barzilay: The person who did MIRAI for his PhD is my student Adam Yala, who is now a professor at Berkeley UCSF. And he came up with this name MIRAI—if I’m not mistaken is future in Japanese. And the idea is alluded to. So people were trying through this density pattern, trying to predict what is there that happens in the tissue before we can actually see cancer? And people try to do it using kind of just analysis, like looking as humans and try to say, “Okay, this is a bunch of women who didn’t have cancer. That’s how their mammogram looked few years before. And this is the women who did get cancer. That’s how their mammogram looked like.” But it’s a very imprecise. So instead what we’ve done, we gave to the machine images of women, which we knew what happened to them in the next five years.

So the machine would kind of see the images of somebody who doesn’t have cancer in the next five years. It would see images of somebody who would get cancer within two years and images of somebody who is going to get cancer in four years or in five years. And by providing this kind of pairs of image and the outcome, machine can correlate particular features of the image with certain label. And it’s not very different from your iPhone that is trained to identify your face when you want to unlock it. So in this case, instead of training it on your face, you train it just on the image and the outcome. And there are many kind of techniques that you can do to do the better job. But this is a basic idea. You just apply a version of computer vision algorithm that is trained on the patient outcomes and then once it’s trained, once it’s seen hundreds of thousands of examples like this, they can actually go take a new image that hasn’t seen before and give you the likelihood of developing breast cancer in the next few years.

Chris Riback: I know that what you were just describing was the retrospective part of your research and proving out the viability of MIRAI. I’ll ask you in a moment about the prospective trial that you are doing, but given what you just described, would it have caught your breast cancer?

Dr. Regina Barzilay: Yes, so it was very interesting. So after I started working on it, I had my mammograms. It took three mammograms before I was diagnosed and we can actually look back and in my case it’s actually even visible. It’s very tiny, it’s like ambiguous. But if you see the sequence, you see there’s a particular spot that increases over time and something like MIRAI would flag me as a high-risk patient. So the question is what do you do if you are high risk? So you can suggest to this patient to do MRI or maybe do ultrasound or do something. It’s not going to tell you, it can say that it’s already sitting there, but it just kind of flag that says you need to go and do follow up. And I just want to say one of the things that we did, and it was interesting because it was done just before the pandemic.

So very early in the pandemic, one thing that we did for MIRAI was validated across many different populations. We went in the U.S. to Novant [Health] in the Carolinas. We went to Emory University Hospital, we went to Taiwan at the beginning of pandemic to day one I think in January or February in Sweden, in Israel just to ensure that this model actually delivers good results in different population. And the reason you have to do it because human cannot validate it. When human is looking at it, they don’t know whether the patient has or has not. So you need to ensure that the model works well across different groups.

Chris Riback: And I was going to ask you about that because as the rest of us are becoming more educated around AI, obviously one of the things that we all hear about is the risk of bias in various AI executions. It’s no surprise given what you do and the awards you’ve won and the years that you’ve spent thinking and worrying about AI that you factored in or worked in the individual differences that can occur based on culture or race or historical access to healthcare or any other range of social issues. That obviously has to be table stakes in terms of creating an algorithm or a program like what you created.

Dr. Regina Barzilay: I think that for breast cancer when you’re developing AI for this patient certification software, it’s really important to ensure that it works across different groups of patients. For instance, we know that African-American patients develop breast cancer much earlier. It’s more aggressive cancer. One of the challenges––and they talked to many patients, many patients who some of them by chance discovered it or they already had tumor which was growing, and it was before 40 before they even start screening. So first of all, we want to ensure that it works for these patients who really need help. But second of all, we can imagine that looking forward that we can do the first mammogram not at age 40, maybe we can do it at age 30 and then say these patients really look kind of safe and secure and they can come back at 40, but this patient really do not look safe and secure and they maybe should be coming in more frequently.

Because right now the program is that for all of us, unless you have BRCA, which is only 15 percent of breast cancer patients who have this condition. For the rest of us, the recommendation is you come every year since starting at age 40 or there are some people who argue about different frequency in Europe every two years, but we need to have a screening regime which is personalized to your individual risk rather than just look at your age and your genetic status and so on. So I think it’s key for these tools to be really equitable because this is the only way they can make a difference at the population level.

Chris Riback: What’s been the reaction within the healthcare community, within the breast cancer community?

Dr. Regina Barzilay: So it’s very interesting. So when we started working, it took us a while because my papers from breast cancer were the first papers I wrote kind of venturing into medical domain; before I wrote all my papers in computer science venues. It took us a while, but then we start publishing and Adam Yala recently attended a breast density conference in Hawaii, and he related to me an interesting conversation. He said a big portion of papers there were actually trying to check how MIRAI works in different population in different settings. So it’s good to see that people are trying it and independently validating it. But what he said, which was kind of interesting, that when we first published our paper, it was I think at a 2019 radiology conference said that they didn’t believe our results because it looks so good.

Chris Riback: Wow.

Dr. Regina Barzilay: And now that they validated it and there are more and more results coming it’s changing, but it’s not easy because now we are after, again, paper was first in 2018 to today we’re in 2023. We are in a better shape in terms of people accepting it, people talk about it. It’s a known thing, but still it’s not part of the routine clinical care and it’s not unique to only breast cancer. We see very few AI tools in our routine. This is an interesting question, which is maybe not necessarily a pure scientific question, but more implementational clinical question. How do you take it, some things that work in many research studies, how do you really translate and make it part of patient care? That’s the question that we are all thinking about now.

Chris Riback: And to your point, if I understood this part of my research correctly, you’re also applying your work now to lung cancer risk.

Dr. Regina Barzilay: Yes, absolutely. So we actually did the paper and it actually works even better on lung cancer because you use CT scans. CT scans, it’s a higher-resolution modality than mammograms. And it works reasonably well. And when it predict that the patient has cancer, it also has a chance it’ll tell you on which lung it’ll be located. So what it tells combined, thes two pieces of evidence that we’ve collected is that maybe the malignancy should grow to sufficient size and have some significant impact on the tissue so that human eye can distinguish it. So, when we are thinking about risk, when we’re talking about BRCA gene, a girl may not even really have breasts, she can be very young, but she still has a higher risk of developing breast cancer. Talking here really about risk. Here we  may be talking about the patients where the cancer already grows in their breast or in their lung. It’s just machine can predict it much earlier or identify that the patient goes this way before human eye can discriminate it.

Chris Riback: Tell me about you. You grew up in a couple of different countries I believe, or at least spent a few of your initial years in Moldova before leaving. Tell me about you, your journey and was it always science for you? Was there another passion or always computer science and always technology? And I know you’ve got electrical engineering and probably 75 other highly intricate interests and degrees in your background. But was it always that side of your brain or was there ever a possibility that you were going to go and do poetry or creative writing instead?

Dr. Regina Barzilay: I wouldn’t go that far. So I did my undergraduate, I always was interested in math. So I did my undergraduate in math and then I was a teacher in high school in Israel. I worked while I was still doing my undergrad, I was working in high school as a teacher and then I went to study masters in computer science and then eventually I get there. So I’ve never thought of first of all doing creative writing or being a poet and also about the medicine. It was kind of clear to me that it’s not my cup of tea because I’m afraid of blood. But it’s really surprising to see how much now I go to it through this line of research, but luckily I can just do my computer science without observing through patient care.

Chris Riback: Did growing up in multiple cultures, and I guess maybe you don’t view it as multiple cultures. I believe you spent your first five years in Moldova before then growing up in Israel and going to university in Israel. I think then before coming to the US for graduate school. Is there an aspect of that part of your life that you think has affected your perspective and applies itself to the work you do today? Or do you think irrespective of that background you’d be doing what you’re doing today?

Dr. Regina Barzilay: I think that one kind of lesson that I see moving through different cultures. So I was 20 actually when I moved to Israel. Moving through different cultures and kind of observing personally how the Soviet Union fell apart and when they became independent and we moved to Israel and then I came to the States. There are lots of things that we take for granted in our daily life just because it’s something you don’t even question. When you are moving between different cultures, actually some things that in one society are norm. In other society, they’re totally not normal. In some ways, it gives you more courage to try things that others didn’t try. When I started working in this field, when I was literally going to people, who I barely knew at [Massachusetts General Hospital] and saying, “I would like to walk with you, I’m a computer scientist and I’m a breast cancer survivor, can you please work with me?”

And there were so many rejections and people say you don’t know what are you doing and go back to your NLP [natural language processing]. And I think that this robustness of you kind of go to different places and you just stand up and try another way that maybe a bit helped me to go through this challenging period—and it was quite challenging. I just want to say how much I really appreciate support of BCRF because for us to be able to move fast and to really bring it to patients, because this is my key motivation for doing this research. It should really change the outcome for patients. BCRF funding enables us to do these prospective studies where we actually are applying it in clinic, seeing how it changes the outcome and observing the results of prospective studies would be a motivation for daily changing the clinical standards, assuming that the result’s as good as we hope for. So this was another piece of success that having an organization that can take your idea however crazy the idea may sound and provide you this support was really essential for us.

Chris Riback: Yes, that is among the many things, but it is a key aspect of the work that BCRF does. To close out Dr. Barzilay, of course, we are all extremely grateful for the historical work that you have done. We are all equally impatient about the future. So what’s next?

Dr. Regina Barzilay: Oh, thank you for asking question. So while we are working, and Adam and I are working, Adam actually more leading this work now in the translation, there is a question that again as a patient I am really, really curious about and that what motivates my new project. So as you know, many breast cancer survivors are taking tamoxifen, which is a drug, and now the recommendation is 10 years of tamoxifen. And depending on the patient, they experience various side effects. Some of them are immediately apparent, some of them are less apparent. There are again clinical studies that shows that if you take it instead of five years, by 10 years, it decreases your chance of recurrence. There are several questions. Is it really benefiting everybody? Because when I actually was starting my treatment, the standard was five years, now it is 10 years.

And the answer is we don’t really have a good answer to this question. We don’t know. Can the patient stop? Maybe somebody’s ready for 15 years, maybe somebody is now five years. There are some different tests like the Breast Cancer Index [developed by BCRF investigator Dr. Dennis Sgroi] and others that try to answer these questions, but there’s still not a standard of care. So, the questions that I’m trying to answer, and we’re just now in very early stages: Can you detect based on your tissue if tamoxifen is still benefiting you? Do you need to take it? And the bigger question is, and I’ve recently discovered by doing a lot of reading that actually tamoxifen penetrates blood brain barrier and it has a long range of effects on your brain. It’s well-documented in scientific literature. And again, the question is can we create another version of the drugs that maybe don’t do it or then they can what does it do to based on your individual makeup because another part of my research today is primarily drug discovery.

So can we create another drug which will be as effective, but at the same time maybe with less undesired side effects? So that’s what I’m thinking right now.

Chris Riback: You are genetically incapable of slowing down is the lesson I’m taking from you.

Dr. Regina Barzilay: Hopefully, hopefully.

Chris Riback: Hopefully, for sure. Well, I look forward to, and I’ll put in my request now, for the opportunity to get to talk with you again as you advance on that new effort. We thank you for your historical effort, your continuing efforts on MIRAI, and thank you for taking the time with me today.

Dr. Regina Barzilay: Thank you. Thank you very much.

We know the age-old expression: We are what we eat. So, how does diet affect or reduce the risk of breast cancer or how breast cancer progresses? And what non-lifestyle choices should one consider when looking to reduce their risk?

Dr. Graham Colditz, a BCRF investigator since 2004, has spent decades diving into these questions and more. Dr. Colditz is an internationally recognized leader in cancer prevention and one of the one of the most highly cited medical researchers in the world.  

Not only has Dr. Colditz published more than 1,100 peer-reviewed publications and six books and earned numerous awards, but he’s developed the widely-cited website, Your Disease Risk. At Washington University in St. Louis, he is deputy director of the Institute for Public Health, the Neiss-Gain Professor in the School of Medicine, chief of the Department of Surgery’s Public Health Sciences division, program director of the Master of Population Health Sciences degree, and the associate director of prevention and control at the Siteman Cancer Center.

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

Dr. Graham Colditz: My pleasure being with you today.

Chris Riback: So, I read a write-up about the impact you seek to make through your career and area of focus. And the first sentence of that impact statement reads, “It is estimated that nearly a third of breast cancers could be prevented by lifestyle choices, particularly those that support and maintain a healthy weight, including diet and exercise.” And I confess that made me feel really good and somewhat not so good. The not so good maybe is obvious. The sadness that so many people suffer based not purely on genetics, but rather lifestyle choices. The good part: it would seem that cancers resulting from lifestyle choices can be preventable through the help of scientists like you and personal actions. So help me please doctor, should I be feeling lousy or hopeful or both?

Dr. Colditz: Oh, I think both. And I can say a little for both in that it’s clear some of our risk can be set fairly early in life. And so we are not thinking about cancer as children or adolescents, so that’s maybe personal choices, peer pressure, and so on, that changes a little how much control we may have. But at the same time factors later in life that we do as adults and free-living have definitely more control over, whether we have complete control, whether the social-political environment we live in doesn’t tax alcohol, as much as you and I might want it to be taxed to cut down our easy access.

Chris Riback: Access. Yes, sure.

Dr. Colditz: Yes. But it’s that spirit.

Chris Riback: Understood. So help me, if you would level set on the science and how one derives conclusions out of an area where again, for an outsider, one can hear the numbers and you want to understand, so how does one actually get to those numbers? We can get to some of the root causes and effect. So, you derive the statistics, and I’m curious how one does that generate a statement such as, “It is estimated that nearly a third of breast cancers could be prevented by lifestyle choices.” What is the scientific discovery process look like? How do you “prove” that? And to what extent? How do you factor out or consider the role that genetics play and to what extent they’re tightly connected to so-called lifestyle choices, like healthy weight? Sorry, there’s a lot there.

Dr. Colditz: Yes. Unpack decades of works. Right.

Chris Riback: Yes. In 30 seconds, if you could, and if you could give a clean in and a cleanout that would really help.

Dr. Graham Colditz: Yes. So, the simplest concept of this would be to identify a set of say, women in this case [since] we’re studying breast cancer, who are at very healthy lifestyle: healthy diet, say no alcohol, average weight. [We] follow them over time and follow a group that is high risk: heavy drinking, overweight, and so on. And we can compare the difference in the risk of breast cancer between the two groups and do the arithmetic to estimate what proportion is avoided by following the healthy lifestyle. Then you raise genetics. So, we have to then factor in family history, say, and we can look in women with no family history and see these same effects. So the statistics and the inference from both the human data there often to get to the cause and prove words that you were asking. We want to see bench science, animal models, other hormone levels mechanisms that actually support the association.

So, when we look at alcohol and breast cancer, the International Agency for Research on Cancer concludes that alcohol causes breast and a whole range of other cancers. They’ll look at the human evidence [and] the animal and other sources of evidence to lay out a mechanism as to how alcohol is actually causing cancer and how it’s doing that in the breast.

Chris Riback: And as you go through that science, and so much of your work caught my attention, but this component that choices made even in childhood and adolescence can impact a person’s future risk of breast cancer. To exaggerate the point, it can get hard to get an adolescent to stop watching TikTok, to do homework, do the next day. How do we start to talk to [our kids about this]? How does one convince her to sleep more now to help prevent breast cancer in 20 years?

Dr. Colditz: So, you’ve hit a really important point that a lot of the lifestyle in childhood and adolescents won’t be framed in terms of just breast cancer risk. It’ll be for your health, for your future health and adolescents aren’t always so future-oriented, as we know. But you’re totally right, that again, studies show diet and physical activity—physical activity particularly, say, between ages 12 and 20—actually can have a lifelong impact. So how do we have a society that supports that, rather than thinking it’s just TikTok. Or just the mode of transport so we have access to safe exercise. All of these things I think come together and that will reduce risk of diabetes, heart disease, and stroke, as well as what we’re after, which is breast cancer. Because we don’t have the same range of options for prevention for breast as those other conditions I mentioned.

Chris Riback: There’s one area of your study and please, correct me if I’m misinterpreting this, that also struck me. The benefits to adolescents of eating nuts. Why are nuts such a big deal for adolescents to eat?

Dr. Colditz: That’s a super question. Interesting thing here is that we can look at diet, fruit, vegetable, fiber. Nuts come through as clearly reducing risk. My colleagues at Harvard had studied nuts in relation to other diseases, right. But the assumption at this stage is still that nuts are uniquely good at changing your metabolic profile. And that this in fact then is translating through to breast cancer risk. I don’t think we’ve got all the fine details of mechanisms nailed down, but it’s consistent across multiple studies. And again, fairly simple part of lifestyle, if you will.

Chris Riback: And another area into which I understand you plan to dive deeper: how modifiable factors such as diet affect or reduce the risk of breast cancer, including how those factors affect the rate of transition between breast cancer stages, such as the progression from benign breast disease to breast cancer. Where are you on that work? I couldn’t fully determine whether this was a gleam in your eye or whether you were deep into the research. So tell me about this please.

Dr. Colditz: Very cool. We’re actually writing a grant literally as we speak but over multiple weeks now, to really further understand which factors are impacting sort of, if you will, the age at onset of the first lesions, the premalignant changes, and which factors are driving subsequent speed of growth, transition from benign lesions to invasive or in situ and then invasive disease. And the irony in much of our insight on prevention is that we don’t always have a very good sense of the timeline of when a change in lifestyle will actually finally translate to our risk. Okay, for smoking cessation and heart attack, we know that’s a very short cycle, but obesity and cancer, [there are] lots of different ways that this can be changing risk. And so it will help us focus and identify who’s going to benefit most from the changes for prevention.

So grant pending, colleagues working with me on statistical methods to improve the way we can look at this. Building on our premalignant lesion repository that we’ve got. So there’s a number of ways to come at this. So it’s moving, maybe not as fast as we’d all like, but it’s beyond just a glimmer.

Chris Riback: Picking up though, just on one of the elements that you said: What inspired the choice or the decision that there is a need to look at that? Was there a gap perhaps in data that you had noticed? Was there new data that came across or was this an area that you or colleagues had always wanted to look at, but now just it so happens that the time is right?

Dr. Colditz: No. So, one of the concerns I’ve had with recommendations about prevention—going back 30 years of teaching on this—is that we often end up with recommendations, if we act now we can halve cancer mortality in 10 years. And you’re like, “Really?” Is it all going to change that quickly? Right. Our sense to engage people where they’re at with the level of risk they’re at, we have to have realistic sense of what change will lead to risk reduction [and] over what timeframe. And that just trying to bring more clarity to that is really motivating this. And so it is right in front of us to be done still.

Chris Riback: One more question on the science components, and then I want to get into… Yes, I have the privilege to do a number of these conversations. And in preparations for this conversation, I did get many questions around the, well, what should I do here? What should people do here? So, yes, as you know from the questions that I know you get peppered with all the time, people do want those tips from you. So, I’m not going to let you off the hook. I am going to at least ask you for those tips. But one more question to connect really the science, the biology, and the behavior. How does something like obesity or diet or sleep, even connect with something as specific as breast cancer? What is that path? How do those dots actually connect?

Dr. Colditz: So, let’s take obesity after menopause, and for weight gain, which of course is the trajectory most of the world is on. We know that the more overweight a woman is the higher her estrogen levels are—estrogen active, if you will—as a fertilizer for cell division and cell division can lead to even more genetic damage accumulating, right? So that one is in fact, very, we’ll say simple, and we can compare U.S., Japan, other countries that have different weight gain trajectories and see a substantial portion of postmenopausal breast cancer can really be explained by this higher obesity, higher hormone exposure, and higher breast cancer.

Chris Riback: Now to get back to putting you on the hook. We got a number of questions that folks would like in terms of helping guide their personal behavior. I imagine that you might have various caveats, please feel free to let me know about them, such as each of us is different. And each of us should discuss our personal situations with our personal physicians. And the other caveats please add, of course. But if I could ask you some of these to begin, are there any foods that are proven to reduce your risk of breast cancer? Is there such a thing as a breast cancer-fighting food or a breast cancer diet, even?

Dr. Colditz: Not a specific food, but the fruit and vegetable cluster still is probably the most promising part of diet for prevention of breast cancer.

Chris Riback: And you just mentioned estrogen a moment ago. But what’s the link between estrogen and the food that you eat? Are there foods that can lower or increase the estrogen in your body? Because you’ve already talked about the effect that estrogen can have in terms of risk of breast cancer.

Dr. Colditz: So, the challenge for the foods lowering estrogen really comes down to separating out the foods and weight, right? But the potential is there for a higher fiber diet to actually be helpful in the steady hormone status. Higher physical activity is probably working in that direction too. But a specific food is not going to change hormone levels up or down on its own. Maybe alcohol has some impact separately where it’s a chemical agent if you will. That’s very different from trying to think across all the foods I eat, which chemical am I getting with alcohol? We actually know what we have. Yes.

Chris Riback: You’ve mentioned alcohol a number of times, but is that primary or close to primary on your mind in terms of things that you worry about in terms of lifestyle choices?

Dr. Colditz: Both in terms of lifestyle choices and how we could counter its effecting the breast. Yes. For a long time, we’ve puzzled over whether there are the equivalence of the vitamin you could take that would counter the effect of alcohol. We have colleagues who say, “Well, just stop everyone from drinking.” And it’s like, I think we tried that as a nation once, right?

Chris Riback: Yes.

Dr. Colditz: And we know that adolescents and college-age women have caught up to men with their alcohol consumption. So the trends are probably going in the wrong direction for breast cancer. So, what are the potential ways to A) control the amount of consumption and then B) if there are women who are continuing to drink, how do we find strategies to counter that effect? And that’s still an open question.

Chris Riback: What about breastfeeding? Does breastfeeding “prevent” breast cancer? What do researchers know about the link?

Dr. Colditz: Yes. So, we’ve looked at the analysis of all the published studies and definitely there is a reduction in risk for women who have breastfed, and the longer they’ve breastfed the lower their personal risk. This relates to changes in the breast tissue that are in fact, a consequence of breastfeeding. The good news is there’s benefit. Again, the bad news, our social structure, there are workplaces where breastfeeding is really hard, if impossible. And so we can think of this as, yes, it may be an option for some women. It’s not, I would say, an option for every woman given her work and social circumstances. So, you could argue collectively we should be providing more support for breastfeeding if we care about this as a nation. But yes, the changes in tissue, lifelong benefit, more is better in this case, even though, as we have fewer and fewer children that is diminishing returns.

Chris Riback: Yes. Population demographic changes are very, very significant. I think the last question I have on the tips from Dr. Colditz section of this conversation. You mentioned exercise, of course, and we all hear, read about all the ways in which exercise, even very little bits of exercise can be beneficial. Any other non-lifestyle choices that someone should consider to reduce their risk of breast cancer?

Dr. Colditz: I would put in there as well, avoiding further weight gain rather than thinking we’ve all got to go back to whatever weight we were in high school or somewhere that is, we’ll say, largely unattainable. If we all avoided more weight gain in 10 years’ time, the nation would be leaner than if we all kept gaining one to two pounds a year. And so setting a monitoring—self-monitoring scales and paying attention to weight—rather than what we may do as a nation, [which] is new year’s resolution, try to lose weight, give up, gain it back. It’s a seesaw that keeps going up.

Chris Riback: What an excellent way to frame it. So the idea of losing weight, getting back to that college weight or whatever is so intimidating. It makes it so easy to give up. Instead, to frame it as. Just maintain. It’s much more attainable, just much easier to consider. Tell me about the Your Disease Risk website. What is it? How should people use it? What kind of impact does it have? Is its impact educational or on actual behavior?

Dr. Colditz: Oh, that’s really great question. So quick summary, the website was developed over 20 years ago with a goal of helping people understand that cancer is preventable. The thought process in the 1990s if we can go back that far before COVID. Sort of this, well, there’s nothing I can do. And we put the evidence together, worked out how to communicate that to the general public and developed a tool that is engaging and offering tips and strategies to adopt changes in lifestyle that can lower risk. And so, it’s used. It’s engaging and really takes account of where you are at now in your risk factor profile as to suggestions for changes. The ability for it to transform people’s behavior overnight just by using the tool once is wishful thinking.

Chris Riback: Yes. Yes.

Dr. Colditz: But definitely, it’s been used in studies by colleagues, either a component of it, or more to promote more discussion with your primary care provider about risk and risk reduction strategies—things like this that show it actually is engaging women, and having them engage in more discussion of prevention. I think they’re all steps towards successful changes to lower risk. And there are certainly people who come back multiple times. So lots of pieces to support that it’s beneficial, but we can’t say, if you go use it tonight, by the end of the month, you’ll have moved your risk down.

Chris Riback: Well, you do understand doctor, we live in a time of immediate gratification. If not by the end of the month, certainly by the end of next month. You can guarantee that, right?

Dr. Colditz: There you go. There you go.

Chris Riback: Thank you. So it is hard to have the privilege of getting to talk with you and not also ask about your landmark work from now more than 25 years ago. You helped identify the increase in risk of breast cancer with the use of combined estrogen plus progestin therapy and a significant increase in risk with increasing duration of use.

Dr. Colditz: Yes.

Chris Riback: You also showed that mortality from breast cancer was also elevated among current users. How do you look back now on that work and the incredible impact that is made?

Dr. Colditz: That’s a super question, and it’s gratifying that the results held up. The Women’s Health Initiative trial held up and in further evidence that’s accumulated [in the] UK and elsewhere. The continuing current use is the real driver back at our earlier question. When you stop using that combination, risk starts to fall back to where it would’ve been. So, there’s a real effect—it’s reversible in large part. And while the manufacturing industry for tooth and nail to, if you will, discredit some of this and assemble data that contradicted what we and other studies obviously showed. The trial stopped early, therefore it must have been wrong. Well, it stopped early because the stopping rule said adverse breast cancer was a reason to stop, right? So people can twist this, but to me it highlights, again, the good data focused on breast cancer can really help understand how the disease process is modifiable. And so we should be continuing to push for other ways to modify this risk.

Chris Riback: Wow. It’s incredible impact to so many people over such a period of time. It’s wonderful. If I could have the benefit of embarrassing you further. I’m curious about where you are now versus your expectations coming into your profession. You grew up in Australia. And as I understand it, growing up, you enjoyed your share of cricket and rugby. And now besides the individual impact you’ve made on individual lives. Do you happen to know what the h-index is? Do you know about that?

Dr. Colditz: Yes.

Chris Riback: Yes. For listeners who aren’t aware, it’s an author level metric that measures both the productivity and citation impact of the publications initially used for an individual scientist or scholar. According to Google Scholar statistics, you have the highest h-level index of any living author. I can only assume that that was your exact expectation set as you got into this, wasn’t it?

Dr. Colditz: Not at all. And it’s a moving target, who’s at the top. Right? But it’s a great question. In med school, I really wanted to do prevention. I did oncology rotations where you had lung cancer patients that clearly had been smoking. And we didn’t talk about smoking cessation in med school, right? And then you do another ward with women with ovarian cancer, and we had, at that point, no idea what’s causing ovarian cancer. And that hands-on experience really pushed me to ask, why aren’t we doing more to prevent this pretty horrible set of diseases? Lung, ovary, breast—my sister-in-law died of breast cancer in her 20s. So it’s really dramatic to see we’ve made a lot of progress. It’s still challenging that there’s so much more to do. But as a med student, it was, I just want to go and some prevention and my mom was upset, I didn’t come back to Australia after I finished my PhD.

Chris Riback: Can’t blame her for that. Factually, she was right. What do any of us want to do? We want to make impact in whatever chosen profession and to have done that and to have that double benefit of knowing that you’re making impact on individual lives, personal lives, but that also it’s getting amplified because it’s being cited, because in the metrics around how it’s being cited. When I came across that fact about you, it just struck me that, that must be a double or even somehow exponential level of satisfaction. Because you’re getting to make impact beyond yourself. It grows through others citing your work. And that’s a nice thing.

Dr. Colditz: In a real way; the mentoring junior colleagues and supporting them is another. We don’t have an index for that, but that is part of the power of this, that the number and range of people and the skills that are coming to prevention clearly has grown over time. And yes, the work is cited, but we’ve got to also move it to the next level to get the changes in behavior.

Chris Riback: Of course. We’re not going to let you rest on your h-index doctor, you know that.

Dr. Colditz: Thank you. Thank you.

Chris Riback: Yes. We’re not stopping there. To close out, if you would, what role has BCRF played in your research?

Dr. Colditz: Well, they’ve been an amazingly steady support for our work, and I will say unique support for our work to look at this childhood and adolescent exposures and breast cancer. We’ve tried to get NIH funding for this on and off over the years. And the peer review process is skeptical of that. But BCRF has been there through the whole of this, and if you look we’ve contributed substantially to the literature on the adolescent diet activity and so on, early on that others have then tried to replicate in other studies. And BCRF was in there at the beginning of this and to this day continues to support us to build on both the adolescent piece, but also now more on the premalignant lesions and how they progress and what we can do to modify that. So, we wouldn’t be where we’re at without that support over the years.

Chris Riback: Well, that’s kind of you, and I’m sure that what folks would like now is for you to get back to the grant writing, figure out this leisure thing, and keep pushing your h-index and the impact that you make. Dr. Colditz, thank you. Thank you for your time. Thank you for the work that you have done throughout your lifetime.

Dr. Colditz: Chris, thank you. It’s great to be here. And thanks to BCRF for all the support.

Effective medicine has always relied on clear and verifiable diagnoses. Of course, for patients, the wait and uncertainty of diagnostics can be especially trying.

Dr. Connie Lehman is among the scientists and practitioners trying to change that. And she’s doing it in myriad ways—from leveraging both new technologies like artificial intelligence (AI) to conducting old-fashioned operations management fixes—to drastically reduce wait times and detect cancers earlier.

With more than 250 peer-reviewed publications to her name, Dr. Lehman has led meticulous studies of advanced imaging tools to identify breast cancer at its earliest stages—when it’s all but guaranteed to be cured. Dr. Lehman, a BCRF investigator since 2019, is a professor of radiology at Harvard Medical School, and chief of Breast Imaging and co-director of the Avon Comprehensive Breast Evaluation Center at Massachusetts General Hospital.

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

Dr. Connie Lehman: Oh, thanks for having me. I’m glad to be here.

Chris Riback: So, let’s start with the area, the word, the procedure, that everyone knows about, mammography. Is mammography still the gold standard? What are the benefits of mammography and other imaging techniques? And what do you wish were better about the process?

Dr. Connie Lehman: You know, it’s so interesting, because almost every new grant that I review or read, in the area of early breast cancer detection, they start by talking about the challenges of mammography, and we all know those. There’s human variation, some people are really great at reading mammograms, others can miss cancers that are on the mammogram, there’s a lot of human variation. We have challenges with access, any women will tell you that she doesn’t look forward to having her mammogram, the compression, women have concerns about the radiation. So it is a test that’s fraught with challenges, but it is absolutely the best method we have to detect breast cancer early when it can be cured, so we’re working very hard in all kinds of domains [like] liquid biopsy. Wouldn’t it be great if there was a blood test that could let you know whether or not you needed more intervention or whether or not you were harboring a small, tiny pre-clinical breast cancer? So, a lot of fantastic research, but at this time, without any question, screening mammography is the best tool we have to detect cancer when it can be cured.

Chris Riback: One of our recent conversations in the series was on liquid biopsy and yes, that would be fantastic. Not wouldn’t it be, won’t it be fantastic.

Dr. Connie Lehman: Exactly, it will be.

Chris Riback: It will be. As we’re waiting for that, what is an immediate-read mammography, and how in the world did you and the team reduce the median time to report finalization from 61 minutes to just 4 minutes?

Dr. Connie Lehman: So, I love that you asked the question, with what my team and I did, because it took a team effort. It was really our entire community of our administrators, technologists, our fellows in training, our faculty saying, “We need to do screening mammography differently for our patients.” What really stimulated us to start thinking differently was the pandemic, and many people have talked about the challenges of the pandemic. But that silver lining, where we all found we could be more nimble than we realized, and we could tackle some of our challenges, they were actually there before the pandemic, but that the pandemic sort of opened our eyes to the problems. And one problem was the differential experience that our patients had in that first screening that would show an abnormality, to the final diagnosis of cancer and becoming engaged in treatment. And those differences we saw across our patients were really worrisome to us, and we feared that they were getting even more exacerbated with the pandemic.

So, we decided to do something about that. We said, what if we could treat every single patient that came through our doors for a screening mammogram as a VIP. Let’s make sure they have their result while they wait, if they need more imaging, whether for a simple technical repeat or for actually an evaluation of a lesion, let’s just do it while they’re there. Let’s change our workflow, let’s work together as a team to figure out how, rather than having the patient go home and have that screening mammogram sit on our pack station, where we store our images, waiting for a radiologist to review it. What if we flipped it all around, made it totally patient-centered, and said, “We’re going to read these real-time, immediately, while the patient’s still there.” So, for that percentage of patients that need more, more imaging, more workup, we do it right then rather than have them come back, days, weeks, unfortunately for some of our patients, even months later.

And so that’s what we did, and it was really fantastic, not just for our patients, for individually, for them to be so grateful. But also we completely eliminated the disparities we had seen before this program, across differential races and ethnicities in our patient population.

Chris Riback: Why is that? What happened there?

Dr. Connie Lehman: Well, we found out that before we implemented our immediate read screen, the amount of time for patients that we had, our patients of color, whether they were African American self-reporting as Black, Asian, Hispanic. The amount of time between having an abnormal screen and having that confirmation of a breast cancer diagnosis was significantly longer than for our white patients, and that really concerned us. And we have lots of hypotheses on why that might be, but we just knew that it was there. A lot of groups have said, well, we need to educate these groups better, they need to understand the importance of coming back in. But how amazing when we just changed our workflow that we got rid of the problem. So, it became something where we thought, Oh that’s something where you can actually change the system, rather than expect the individual to change their behavior.

Chris Riback: As an outsider, listening to this, among the things that struck me as so remarkable. So we all think about, what can be the breakthroughs in improving breast cancer diagnosis care, all of the things that you were talking about, and we all think about. I think about the extraordinary innovation that is going to take millions of dollars and years. And we do need all of those, liquid biopsy, I mean, there’s an example. And yet still while doing that, there are the things that can be done thinking about workflow. It’s almost like a Harvard Business School case that you just described. Like, how can we improve the internal operations of our manufacturing plant, and on some level, that’s what you did, creating a tangible difference in care, without tens of millions of dollars and five to 10 to 20 years of research.

Dr. Connie Lehman: You know, I’m so glad that you’re highlighting that. In fact, we should do a little shout-out and kudos to the Harvard Business School. Because I was fortunate to take a year-long program for healthcare leaders at the Harvard Business School, and it was exactly what you said. It was like these case studies where someone would say, “Well, wait a minute, can’t we do this better, can’t we just change and question the way we’ve always done things and do it a little bit differently.” And, certainly, in other industries out of healthcare, we have innumerable examples of people just thinking differently and really having that, customer-centric approach. And we’re bringing a lot of those processes and those paradigms and those approaches, into our healthcare system. It’s been really exciting to see how quickly a group can actually change their thinking and change the healthcare delivery paradigm or model.

Chris Riback: Yes, the mindset. But what happened on the workflow change that we were just talking about in the immediate read mammography? What happened to the accuracy as you cut the time to final reporting?

Dr. Connie Lehman: Well, this is a great question because many radiologists who I had talked with said, we’re a little bit worried that if we’re doing immediate reads, we might get a little stressed, we might be tempted to race through looking at the mammograms. We might get distracted, someone needs us to go do a biopsy or to look at a diagnostic mammogram. And when we read our screening mammograms, we are not distracted, we’re doing it in batches and we don’t have anyone else bothering us. So we set up our immediate read using those same critical elements of the best reading conditions. So, our radiologists that are reading the screens in real-time, they’re in a room where they close the door. All they’re doing is reading the screens.

We also have these monitors up. So, all of us that are in the clinic that day can see the unread screens, and if the number starts to creep up, [say if] I’m doing diagnostics, I can jump in and read a few of the screens real-time. So, it was not just saying, “Well, we’re just going to start reading these as fast as we can.” It was actually building a full system to support all the good things about, quiet, protected, batch reading, but timed so that it was happening while the patient was still there.

Chris Riback: Interesting. Part of me is wondering, did changing the operations, and cutting down the time dedicated, or available to that read, or focusing the time, I guess I should say, on the read. Did that change the mindset of the people reading it? Maybe you were even more focused, because they knew that they were trying to do it in a tighter period? Anyhow, for all the Harvard Business School professors out there listening, I think we’ve got their next case study and, get ready Dr. Lehman, now you’re going to get to be the star of an HBS case study. Unless they’ve done it already. Have they done it already and I’m late to the game?

Dr. Connie Lehman: No, no, not yet. Yes, we definitely should. And I do like it. We’d studied very carefully, and published our findings and our results, showing that our accuracy was equivalent. That we weren’t calling back more patients, we weren’t seeing fewer cancers. But that we have the same performance level, and obviously that’s critical for this type of program to be successful. So we didn’t have that downtime, where the images were just sitting in our storage system with nobody looking at them. That’s where we really adjusted the timing.

Chris Riback: Thank you for clarifying. Let’s turn to AI. What role does AI play in breast cancer detection? How does it work in terms of identifying personalized risk?

Dr. Connie Lehman: So, I am obviously incredibly excited about this revolution in healthcare with artificial intelligence, the possibilities are limitless. We have had such an exciting two decades of what I refer to as -omics. Genomics, proteomics, radiomics. We have so much data, so much information, but all the information was outpacing our human ability to analyze, to process, and for me, as a radiologist, certainly for my human eyes and my human brain to be able to take in. And thank goodness along came the unbelievably fast computers, and the entire revolution of artificial intelligence and deep learning, and we’re leveraging those tools to have the highest impact as possible on our patients. And it’s going to be in every domain, from risk assessment, to intervention, prevention, early detection, diagnosis, treatment, returning to surveillance. But it’s going to be up to us humans to use them well, and use them with a real attention to rigorous science, to quality, to equity, to all of those things that we’re trying to carry forward in this revolution, in this new domain.

I think one of the things that’s challenging whenever there’s something as exciting as AI, is everyone can a little bit get ahead of themselves. So we have some claims out there that, computers are reading mammograms better than radiologists. This is still early, it’s mainly retrospective studies, reader studies. We all learn from the story of CAT and mammography, that reader studies don’t always translate over into actual clinical practice. So we’re not going to repeat those sort of sins of the past, and we’re going to do this in a really smart way.

The specific area that’s so exciting for me with AI, is risk prediction. So we’ve always been using the mammogram to try to find a cancer. But as a mammographer reading mammograms all the time, I always notice the things you can tell about a patient from her mammogram like, oh, this is a woman that has actually gained a lot of weight since her last mammogram, or wow, this woman lost weight since her last mammogram. We can see that the woman has had a prior needle biopsy, or an excisional biopsy, or even cancer treatment. We can see that a woman has started to go through menopause. Maybe she’s gone on chemo prevention, or maybe she started hormone replacement. Maybe she’s lactating, all of these different factors and features, which we know influence the breast tissue, and impact the risk of future breast cancer. We can see that on the mammogram, but all I could really do is observe it.

But now with deep learning, we’re taking that data out of the digital mammogram, and we’re using it to predict a woman’s future risk of cancer. And that has been incredibly exciting for us to start to explore, it’s something that the Breast Cancer Research Foundation has been equally enthusiastic about. Not only allowing us to do investigations in new domains, novel applications of AI that others aren’t doing, but also create those environments for partnerships. So we’re not just doing this with, amazing computer scientist at MIT and fantastic breast imagers at Mass General Hospital. But also medical oncologists, surgical oncologists, epidemiologists from all the different groups and teams that the Breast Cancer Research Foundation brings together.

Chris Riback: Yes, cross-disciplinary work. These conversations that I’ve been so privileged to have with people like you, so often that’s what comes up.

Tell me, my understanding is that the study that you are working on, the one that you were just talking about. I don’t know if you are still in year two of three, if you are now in year three of three. You’re taking, if I understand correctly, a collection of digital mammograms from the participants of the Nurses’ Health Study II, which I think is data that I’ve talked about previously in other conversations. And this pilot study, you just talked about, that it’s predictive, and you talked about the model. How did your colleagues, your team create the model? How do you anticipate what the model should show? You talked a little bit about some of those factors. And what are you finding? I know it’s early days, but the predictions that the model is developing, how does it compare with actual results?

Dr. Connie Lehman: Exactly. So well, first your question about what year we’re in. We are in the early phase of our year three. And we’ve been able thankfully to make an incredible amount of progress, even despite the pandemic.

So the model was trained on a large population of mammograms that we had within the Mass General system. And then we just, as you said, wanted to evaluate and test it in other data sets. So, an external validation, so Rulla Tamimi and others that were heavily engaged in the Nurses’ Health Study, worked closely with us on this Breast Cancer Research Foundation project, and we learned so much. One thing we learned is some of these older databases of mammograms aren’t what we refer to as AI-ready. It took a lot of work for those mammograms to be saved and stored, but they weren’t always saved and stored in the exact ways that we need to be able to test and train our models, etc.

In research, everything’s not always a win the way we might think, some of the areas where we find it didn’t work the way we thought, it leads us to greater understanding.

I was lucky to have an early, early mentor when I was getting my PhD at Yale. And I would do the ‘Gosh, darn,” when the research didn’t turn out the way I wanted. It was like, this is what’s fun about science. Like it’s, the data are friendly, they’re going to guide you. They won’t always show you what you thought you were going to get or what you wanted, but they’re going to guide you in the right direction. And so Rulla and I just sort of picked ourselves up, brushed ourselves off and said, “Okay, now we’ve learned and know where can we go for the next phase,” and I think that’s going to help a lot of people.

Dr. Connie Lehman: So, we pivoted, and we had partnerships with seven hospitals around the world, and we did our external validation, and we also had a real eye for making sure that we were going to be able to see that this model worked across various races and ethnic groups. And the reason that was so important is we found that our traditional risk models perform extremely poorly outside of European Caucasian women. So for example, Emory was one of our validation partners and almost half of their women undergoing screening mammography self-identify as African Americans. So we were really pleased and excited to see that the model validated very well, had very robust performance at these seven hospitals around the world from Brazil to Asia, in the US, Europe. So we published on that and then we continued to work in other domains, and now we’ve built a very robust infrastructure so that every mammogram at Mass General is processed through the AI model.

And we’re starting to evaluate that now more. Now we’re set up more to do prospective evaluation, which is going to be critical because the bulk of AI work today in this domain has been retrospective studies, and we really need to shift towards prospective evaluation. And then the most exciting, for me, part of this third year is we’re bringing in the other areas of information on patients, biological factors, other tests, very rich databases that we have on patients. Now, we had expected to do this in the Nurses’ Health Study, and we’re still looking at different ways that we can bring that information in. But we also have a very rich source of databases within the Mass General Brigham system, and so we’re pivoting and moving forward into that next level of, what if you had both the biological information about the patient, as well as the imaging information and data.

Chris Riback: And just so that I’m understanding you correctly, that additional data will help evolve and inform the AI model that you will then apply. So you’ll be able to bring in not only that initial set of data, but also this biological data.

Dr. Connie Lehman: Yes. What we’re hopeful is that all of these sources of data are going to be additive. So we can move further in being even more targeted and more precise for each individual woman. Traditional approaches with risk is, you can say, “Well, this whole group of women has a higher risk of breast cancer than this other group of women.” But getting down to being able to tell an individual woman more precisely what her own individual risk is, has proven really challenging.

Chris Riback: Yes.

Dr. Connie Lehman: When we looked at our AI values in this Breast Cancer Research Foundation project, we had the AI values of all of our patients that had undergone screening MRI. And there was a significant group that had known genetic mutations for breast cancer. We were surprised, and I always like it in research when we find something that surprises us because it’s one of those, eureka, a-ha, kind of exciting moments.

Maybe it’s because those women with genetic mutations are on chemo prevention and maybe that chemo prevention, which is reducing their risk, is making their breasts on the mammogram look like, their neighbor that doesn’t have a genetic mutation is bringing that risk down, and we can actually see it with AI on the mammogram. But see it with AI in quotes because I’m not seeing it. So we’re excited about that. It also suggests that there might be multiple sources of information that can help guide us, in more precise prediction, that the genetic information is distinct, does not totally overlap with the imaging radiomics AI-assisted information.

Chris Riback: Yes. I’m curious as well for you personally. I assume that you were trained as a radiologist. You are now getting neck-deep into computer science and artificial intelligence. Is that something that you always were interested in? How has that transition been for you?

Dr. Connie Lehman: Well, when I was younger, I was just interested in everything. In fact, I thought I was never going to be able to decide what I wanted to do because I just wanted to do everything. I was certainly always interested in biology and the sciences and human behavior and the brain. I decided to pursue a PhD in psychology at Yale. It was my first mentor that said, “Ah, you have to combine this with medical training. That’s really what you want to do. I can just tell.”

So, I combined my MD and PhD training at Yale, and then when I was going into radiology, my friends were a little bit surprised because they thought, Oh for sure you’ll be doing the neurosciences or something. They knew I was really passionate about women’s health as well. But for me, radiology’s been just the absolute perfect sandbox to do my work in, because it provides us so many opportunities to have a very high impact on human health and all the domains that are interesting to me. How the brain works, how we change patients’ cognitions and behaviors, and how people make decisions, whether it’s a radiologist, making a decision that a mammogram is normal or abnormal, or a patient making a decision on whether she wants to undergo breast MRI or not. Whether she wants to know more about her risk or not, or if she’s going to come back for a screening mammogram.

So I don’t know, I just keep finding these incredible opportunities. And to me also, my career has always been about relationships. So it was when, Regina Barzilay at MIT had just completed her own treatment and said, “Do you want to work on a project together? I’d really like to make a difference in this domain.” That started this really intense exploration.

Chris Riback: Yes. Well, that would be a hard person to ever say no to. And I assume, I found myself wondering with all of those different interests and potential occupations, French scholar, was that ever on the table?

Dr. Connie Lehman: Do you know, having French as a language never seemed like it was going to bring any added value to any part of my work. Until I was working on a project in Uganda, with some absolutely fantastic colleagues at Makerere University, there in Kampala, and I was walking through the hospital and there was a man who was clearly confused and no one could understand him. And I felt so sorry for him, and the closer I got, then all of a sudden, I thought, Oh, he’s speaking French. And I was able to translate from French to English, with my Uganda colleagues, who then helped the man find out where he was going to go. And there’ve been two other experiences where all of a sudden French was helpful, but many a time I had wished in the US, I’d just learned Spanish way back. But anyway, and then of course travel and fun. French is always going to be a good language to have.

Chris Riback: It’s always good for that. Just to close out the conversation, you mentioned it earlier, but the role that BCRF has been able to play. I know that you’re affiliated with a range of organizations, and you’ve mentioned some of them, and working with MIT and different institutions as well. But how would you characterize what role has BCRF played in your research?

Dr. Connie Lehman: The Breast Cancer Research Foundation has been so critical to the work that I’m doing. And I will tell you, one of the things that really resonates with me is the culture that they set for their community. It is such a culture of inclusiveness, of being excited about partnerships, about being excited about creativity. I’m never worried that when, for example, Rulla and I realized the Nurses’ Health Study mammogram data didn’t work the way that we thought it was going to work, like, “Oh, they’re going to be so upset.” We pivoted, we started to explore other areas. It allowed us an opportunity to do new regions and new areas that we hadn’t even anticipated.

And so that culture of work together, partner together, ask the challenging questions. There’s going to be successes, there’s going to be setbacks, but we’re all in this together. Our patients have been through layer after layer of challenges that we didn’t wish on anyone, and yet you have this organization that the entire time was like, we’re right there with you, and it goes a long way.

Chris Riback: So actually, as we come to the close of the conversation, are there connections? I mean, we talked earlier about the immediate read. We’ve been talking about the AI work, does it all tie together in some way?

Dr. Connie Lehman: You know, it really does, and I’m so glad you asked that. Because it’s easy for us to state our mission statement, that we want to provide equitable access to high-quality healthcare for the full diversity of patients we serve. So we say that, but then we start to think about, well, where do we fall short of that? Certainly when we reopened after we had to shut down during the pandemic, when we found that of our six screening centers, the screening centers that we’re serving our more vulnerable patients were slower to open on Saturdays when more of our patients needed access. And they were slower to open to full capacity, than those screening centers that happened to be in neighborhoods that served our less-vulnerable patients, we knew we had to change. And by studying that, we pivoted quickly, so that early on, we saw those changes and then we corrected by the end of the year. But it really took a lot of effort and a lot of attention that was part of the immediate read screen.

Let’s get more people in and get them fully taken care of. So we don’t have this inequity and who is able to talk their way into, like, “Oh, can you have the doctor read it while I’m here,” and another patient might be less comfortable in asking that, or have a harder time coming back to the hospital. It was a really challenging time. So the whole immediate read screens, we also had our same-day biopsy program looking for equitable access across all of our centers for weekends, for evening hours. That was a big part of the work, but also in the AI, it was so exciting for me to see how the AI risk model worked, and it worked better than our traditional risk models. It was chilling for me to see in my own patients that I feel responsible for taking care of, how inequitable the traditional risk models were.

We found and will be presenting in Chicago at the Radiological Society of North America [annual meeting], that our Caucasian patients are two-and-a-half to three times more likely to be given access to risk prevention, and risk reduction based on the traditional risk models. Even though we don’t see a difference in the rates of cancers in those populations, and that’s really chilling. And there was a beautiful article written in the New England Journal of Medicine, not only tackling these inequities with race across risk models in breast cancer but across everything from renal disease, cardiac disease. So, we have a real opportunity, and I think you may have heard some people say, “Well, we’re worried that these AI tools are going to have even a greater divide in the haves and the have nots, or even greater inequities.” So in healthcare we’ve got to double down and really make sure from the beginning to the end, we’re training the models in the right way. We’re testing them across the full diversity of our patients, and we’re bringing the AI tools into delivering on that mission we have of equitable healthcare for all of the patients that we serve.

So, we see that it all comes together. We’re humans and we know what our mission is, and we are grateful to have so many different tools to make things better, not just for some, but for all of our patients.

Chris Riback: Yes, it sure does, it starts with the patients, as you just mentioned, and then the folks like you. Dr. Lehman, thank you. Thank you for the conversation. Thank you for the work that you do.

Dr. Connie Lehman: Thank you so much. It’s been a pleasure.

Women with breast cancer who are overweight or obese experience inferior outcomes compared to those with normal weight despite receiving optimal therapies. Dr. Vered Stearns is conducting studies to both develop effective weight loss interventions and reveal new information about how weight loss may reduce the risk of breast cancer, recurrence, and death.

Last year, Dr. Stearns and other researchers published a study comparing a remote weight loss intervention (including telephone and web-based tools for coaching and tracking diet, exercise, and more) against entirely self-directed methods for women with a history of breast cancer. Her team found that the remote, actively monitored approach not only led participants to lose more weight but, more importantly, positively impacted biomarkers for breast cancer risk.

Dr. Stearns is a professor of oncology and director of the women’s malignancies disease group at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. She is a member of the BCRF Scientific Advisory Board and has been a BCRF Investigator since 2003.

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Read the transcript below:                    

Chris Riback: Dr. Sterns, Happy New Year. Holiday time and relaxation time seems to often go away quickly. So, I hope you’re still able to reap some of the new year benefits.

Dr. Vered Stearns: Happy new year to you as well. I had a relaxing time, and I’m looking forward to 2021.

Chris Riback: I think all of us are, and everyone has been perfectly happy to say goodbye to 2020, that is for sure. I want to talk to you about your study from last year around how best to do that via remote coaching or through more self-directed measures. But let me start with the concept of weight loss more generally. We know that being overweight can bring various health risks to anyone. That’s why for many of us it’s a new year’s resolution, whether we have breast cancer or not. Are the health risks greater for people either at risk of or managing through breast cancer?

Dr. Vered Stearns: That’s exactly right. As you know, individuals that are overweight or obese are at risk for many illnesses, but in addition to what we’re aware of, such as diabetes or heart disease, people that are overweight or obese are also at risk for several types of cancers. Specifically for the field of my interest, women who are overweight or obese are at a slightly higher risk of developing breast cancer. But more than that, if they develop breast cancer, they are also at risk for inferior outcomes. So this is why trying to help our women lose weight has been a priority.

Chris Riback: As I was researching this and learning more about you and some of your work, I came across the fact that I know you know. I didn’t know this, that unfortunately for various reasons, many women gain weight after a cancer diagnosis, which can increase their risk of recurrence and death of course. Why does that occur? Is it physiological, emotional, behavioral, some mix of all of the above?

Dr. Vered Stearns: There are indeed several reasons why women who have been diagnosed with breast cancer gain weight. Not everybody gains weight, I want to emphasize that, but many will. It’s probably more likely to happen in women who are still premenopausal at a time of their breast cancer diagnosis, and may undergo several treatments such as chemotherapy or receive some endocrine treatment that will enhance menopause, and maybe it will be a more abrupt menopause. So those are some of the women who struggle a little more with weight gain over time. In addition, when women do get chemotherapy, there’s some alteration either in the foods they prefer to eat or with the taste buds or having a little bit less activity, so most women on chemotherapy actually gain some weight. Again, not a lot, and it doesn’t necessarily continue, but they do gain some weight. So this is something that we try very much to address from the very beginning of the treatment course.

Chris Riback: When you say address, do you mean surely from a medical health point of view, but is it as well, you know. None of us likes to feel out of shape. None of us likes to feel overweight, and so I would imagine on some level it is both a physical health risk, but also perhaps an emotional mental burden added on top of what one is already obviously going through. Or am I overstating it?

Dr. Vered Stearns: You’re absolutely correct. Having a diagnosis of cancer is very scary. It’s overwhelming, and there’s a lot to think about and plan. So we really try to first concentrate on the treatment, demonstrating how most women survive their cancer or live for many years with their cancer, and then offer in addition to a treatment plan also what my colleagues and I are calling prescription to wellness. We want women to be able to live their lives as well as they want to. The other thing I remind women is that you might have to undergo multiple different treatments for your cancer, and this will take months or a year, and then you might need to be on hormonal therapy for five to 10 years. So this gives us time for continued dialogue.

So at least what I do, I encourage women to continue to eat healthy and to have regular activity during treatment, because it actually minimizes the side effects related to treatment. But if a woman says, “I’ve never been really very active,” or, “I really know I need to make a change in my diet.” I don’t necessarily ask her to make an immediate change. We start with gradual changes, take a walk around the block or talk to our nutritionist, and then once we go through the acute part of the treatment, then we’ll help her with a more rigorous plan. Indeed, in the study that we’re talking about today, we enrolled women who were about three or so months from their completion of the acute part of their treatment, because we wanted them to be able to focus on this part of continuing to feel well and be well.

The other thing I wanted to mention is that women do really like the idea of getting as much information as possible about other activities that can help them reduce the risk of cancer coming back, and being able to change their diet or change their physical activity or other intervention that can help reduce inflammation is something that can help control and it will help reduce your risk of cancer recurrence.

Chris Riback: Yes, it was just going through my mind and listening to you that having, in a situation that surely must feel so far out of one’s control, to have even minimal tools that one can control or even have the feeling of control has to be useful, and to segue even more into your research, powerful. Let’s pick up on the power. What is POWER-remote weight loss intervention, and how does it compare to self-directed weight loss intervention?

Dr. Vered Stearns: Yes, thank you for providing me the opportunity to tell you a little bit about our work. The POWER stands for “practice-based opportunities for weight reduction.” The very initial POWER study was actually conducted by our collaborators from internal medicine, Dr. Larry Appel, and others who also participate in the breast cancer study. In the initial study, the investigators compared weight reduction strategy, an in-person strategy when the person at high-risk—so in that particular first study cardiovascular disease or heart disease—will come and meet with a coach in person and have their weight taken and vital signs and so on, on a regular basis.

That was compared to what they call a remote intervention, where there was a one-time visit with a coach, and then everything was done through the internet and a phone with a coach. This was compared to what’s called a self-directed intervention, which basically means you provide the patients with educational material and they followed whatever they wanted. If they wanted to try and lose weight on their own, they could. What that study showed was that the patients who participated in either the in-person POWER arm or in the remote POWER arm, both lost similar amount of weight over a 24 month period. You see this result almost immediately within three to six months. Those that were in the self-directed arm had a little bit more trouble losing weight.

So, we board this remote intervention. Basically, we felt our patients are busy. They want to live their lives. We need to help them lose weight, but we need to do it in a way that will be with little interference. What we did in our study was to have two arms. One is the POWER-remote arm, or the patient would meet one time with a coach, and then the intervention will be done via a smartphone or internet-based platform where they can log in their foods and activity and communicate with a coach, and then a self-directed arm. In both arms, patients received the same amount of intervention. In our particular study, the coaching was for a year, and we also collected some baseline, and then over time questionnaires related to mood and sleep and other activities, and also blood samples to look at inflammatory and other biomarkers.

Chris Riback: I want to ask you about the biomarkers and what you ended up seeing there. I’m curious though, what did you hear from the patients, and what did you hear from the coaches? What do the coaches say about the interactions and the feedback that they were getting, I guess, in real-time from the patients?

Dr. Vered Stearns: So let me start with the patients. First, our patients were thrilled to be able to join a study where there’s an intervention, where we’re trying to help them to do something that was difficult for them to do on their own. Part of why I started this study was that I’d sit in clinic with my patients and they’d tell me that they were eating very little, and they were exercising, and they’re just not able to lose weight. I knew they were trying very hard, so we wanted to provide them the coaching they needed. So it was very easy to enroll.

We enrolled patients not just from our site, but we publicized it to the community. So patients were very, very happy to have this opportunity. And to coaches, some of the coaches worked previously on the cardiovascular study I described to you. So, we actually had all educational forum, and I have to thank my colleague, Cesar Santa-Maria, who really developed some of the educational materials where we actually taught the coaches about breast cancer. They knew a lot about weight loss, but we talked to him about some of the potential symptoms or treatments that our patients have gone through that they may not be as familiar with.

Chris Riback: I would imagine for the coaches, it’s very fulfilling to realize that the work that they are accustomed to doing now can be applied as well, and you’re helping find ways to apply that work as well to this potentially whole new population that can get such benefits from their coaching. I would have to assume that’s got to be very fulfilling.

Dr. Vered Stearns: Absolutely. This has been an incredible collaboration that’s expanding. In addition to our colleagues that I already mentioned in internal medicine, we have a behavioral psychologist. We have individuals who are specialized in nutrition and individuals from endocrinology. It’s been a very rewarding collaboration.

Chris Riback: Tell me about the impact on biomarkers. So you went through the study. What was the impact on biomarkers for breast cancer risk and ability to improve patient outcomes?

Dr. Vered Stearns: So, as I mentioned previously, in this study we compared several biomarkers, and we chose biomarkers that are either related to obesity or to breast cancer risk. Many of those biomarkers are what we call inflammatory biomarkers. So some of the biomarkers we looked at are adiponectin and leptin, which are commonly altered in individuals who are overweight and obese. We also looked at lipid profiles. We looked at insulin and glucose and a C-reactive protein. The other maybe more novel biomarker we looked at was telomere length, and what we’ve seen is that has been consistent with other studies. We did see positive changes in leptin, and also modulation in inflammatory biomarkers and lipid profiles. So overall, it suggests that losing weight is good for you in many ways as it relates to heart disease and diabetes, but additionally, you may be helpful in reducing the risk of cancer. Again, perhaps through having less inflammation and less insulin resistance.

Chris Riback: I’m curious, was there impact on the people who did the remote coaching and did the remote weight loss? Was there additional behavioral change or ongoing behavioral change for them even after? Were you able to look at that at all? Did they, in a sense, stay with the program even once the program might have ended, more than the self-directed? I’m assuming that they did, but I don’t know if that was something that you had the opportunity to look at.

Dr. Vered Stearns: In this particular study, we have not looked at benefits beyond one year. But in the previous study I described to you in the cardiovascular disease prevention, we know the benefits, the people who lose weight at three to six months seem to be able to maintain this weight loss at 12 and 24 months. It seems to be fairly sustained. So once you are able to create this change in behavior, you teach people what works for them. What we do here is coaching in an individualized way. Each person has perhaps a different weakness, and we’re able to coach them to teach them how to use different tools to maybe eat differently, or have new methods of physical activity, to create this new balance that leads to weight loss in their situation. So every individual is different, but once you have been able to help an individual lose weight, it seems to be fairly sustained.

Chris Riback: Well, personally, I happen to have two weaknesses, Ben and Jerry’s. It’s both of them. So, you would have to do double work with me, because it’s really both of them.

Dr. Vered Stearns: Part of it is that you should not avoid your weaknesses altogether, but know how to use them in a way that you continue to enjoy your weakness, but also lose some weight while doing it.

Chris Riback: Thank you, Doctor. Now I see why your patients love you so much. I love that advice. Thank you. You’re hired. There’s another personal health wellness area that I understand that you have recently reported on out in San Antonio, and that was on sleep. What did you study? What did you find, and what should we know about?

Dr. Vered Stearns: Thank you for highlighting this recent presentation. My colleague, Jenny Sheng, with other collaborators Janelle Coughlin and Michael Smith have looked at the same patients that we talked about who enrolled in our POWER-remote study. What they looked at was whether they had a sleep disturbance and whether that affected their weight loss. We know that sleep disturbance is very common in cancer survivor and is associated with obesity, suboptimal eating behaviors, and metabolism. So what we did here, we looked at people who reported poor sleep at baseline, and then we looked at whether they were able to lose weight in a similar fashion.

What we found was that patients who had poor sleep were having more difficulty losing weight. My colleague, Dr. Coughlin, actually has an ongoing study right now, which is also supported in part by Breast Cancer Research Foundation, where all the patients received the six months intervention, the POWER- remote intervention. But prior to the weight loss intervention, they’re randomized to an eight week sleep intervention or not. So we’re trying to figure out whether helping people sleep better before they’re starting the weight loss strategy will be helpful. So we’re looking forward to reporting that in the next year or so.

Chris Riback: That will be very interesting to hear about, and it’s another resolution. Among the things so interesting to someone like me about your work is you’re hitting on these wellness areas that we all think about, and we all know that we should be doing. We all know we shouldn’t be eating seven pints of Ben and Jerry’s, to exaggerate the point, but we know that being fit and carrying extra weight is a negative thing. We know we should be sleeping better. To be able to tie that directly to the physical benefits and the biomarkers that you’re talking about for breast cancer, it has to go back to one of the points that you raised at the beginning. Very, very empowering. There’s so much about it that we can’t control. Here are some things and some tools that can put some aspects of it, with help, a little bit back into your control.

Dr. Vered Stearns: That’s absolutely the message that we’re sharing with our patients. We don’t always have an explanation of why one develops breast cancer. We have some medical treatments that will be helpful, but the additional wellness strategies can help even further, and that’s absolutely in their control.

Chris Riback: Let me ask you about the patients and your patients, because I read a great quote of yours. You were talking about physician scientists, people who move seamlessly between the laboratory and clinic, between the science and the patient. You said, and I’m quoting you here, “I was impressed not only with the breadth of their scientific knowledge, but even more so with their ability to translate state of the art research into the specific context of patient treatments.” Why does that combination speak so strongly to you?

Dr. Vered Stearns: As a physician, I want to continue and provide the best possible treatments and hopefully cures for our patients. I know that what we have available to us today is still limited to some degree, don’t get me wrong. We’ve had amazing, amazing advancements in the last few years and decades, but still some individuals will have a breast cancer recurrence, are diagnosed with advanced breast cancer or other types of cancer for that matter. And would die after disease. Even if they live with it for years, this is something that influences every day of their lives. So I’m hopeful that we can continue and improve outcomes across the continuum of breast cancer. To do that, I feel that we need to bring new scientific discoveries from the laboratory to the clinic.

So the example we talked about today, here we have a weight loss intervention, but what we’re trying to do is learn, why do some people lose weight? What we didn’t mention is that about half of the women lost at least 5 percent of their weight and the intervention arm, but about 50 percent did not, and those women worked as hard. So what is it? Is there something biologically different, or are there other parameters? We just mentioned sleep for example, or a biomarker that can help us tell women better whether they’re going to be able to lose weight with a behavioral strategy, or whether they need something else. To help us with some of these answers, we work with amazing laboratory scientists. In this example, Dr. [Dipali] Sharma did most of our cytokine work, and Dr. [Mary] Armanios did some of our telomere work. So lots of people were thinking about the same problem, but from a different perspective, and I think that that’s going to bring more solutions and more cures and discoveries.

Chris Riback: We certainly would hope so. I’m curious as well about you. How did you get into this? I mean, going back, where did you grow up? For you, was it always science? Was it always research and medicine? Did you ever think, perhaps, that instead you’d be a fiction novelist or world-class skier? How’d you get into this?

Dr. Vered Stearns: I always wanted to be a physician. My own memory is to the age of five or so when my grandfather was in the hospital for many weeks, and my mother was one of the primary caretakers for him. I spent lots of time observing the amazing teams that took care of him, and it inspired me to be a physician. I thought he had lung cancer and died of that cancer, and whether that story’s exactly right or not, I cannot ensure, but it inspired me to want to be a physician. And then I was always strong in sciences, and was able to attend medical school, and always was interested in oncology.

When I started doing my clinical rotations, that interest even increased, because what I liked about oncology was that you are specialized, but you’re also become the primary care physician, if you will, of that patient. You get very, very close to the patient, the family. So are you able to have this close relationship while also being a specialist. And then during my fellowship, this is when I really decided that I wanted to pursue breast cancer related research, and my clinic on breast cancer and this by working by other Breast Cancer Research Foundation recipients, Marc Lippman, Dan Hayes, and Nancy Davidson. So I’ve been inspired by working with them to continue their legacy and improve outcomes of those living with and beyond breast cancer.

Chris Riback: What do folks like me just not understand? What part of the battle to cure breast cancer do you wish perhaps people heard better or understood more?

Dr. Vered Stearns: The way I think about breast cancer today has really evolved over the two decades that I have been practicing. Years ago, we thought of breast cancer as maybe one or two diseases, but since that time, we understand that there are several subtypes of breast cancer, and even within breast cancer, there are multiple subtypes. So what makes it challenging is that many of our studies focus on the larger subtypes, if you will, and now we have to get a little bit more specific into those smaller categories within the larger categories. this is where it becomes more difficult, because even though breast cancer is relatively common in Western societies, when you need to do those various specific studies, you really do need to conduct those over many sites and centers. Some of our most important studies have been international in nature. So this is very challenging.

The other thing that people need to know is that it takes sometimes years to conduct and report results. This is even more compounded in studies of prevention, cancer prevention, because even though you might be delivering an intervention and comparing it to some control, you need to wait years to count the number of cancer to develop, to know if your intervention benefited people. The number of individual expense that goes along with it are just very large, and that’s been one of the most challenging type of studies to conduct.

Chris Riback: Yes. Time and patience are hard, very hard under normal circumstances, surely even harder under the circumstances that you’re trying to do research on. Dr. Stearns, to close out, I’d be remiss if I didn’t ask. BCRF, what role have they played in your research?

Dr. Vered Stearns: The Breast Cancer Research Foundation has been instrumental in my research over the years in several ways. First and foremost, of course, is the funding that allowed us to conduct series of studies. I’ve described at least a couple to you today, but over the years, we’ve conducted several studies. Those are types of studies that are difficult to sometimes get funded or to do in a comprehensive manner with some of the more traditional federal base agencies. So what the BCRF has allowed me to do is to trust that I can deliver on what I told the BCRF leadership I can do, and then I can take those results and create or design larger studies, and bring other grants to support the work. So leveraging the initial fundings from BCRF and provide that additional support to new studies, and this has been really an incredible resource over the years.

The second thing is by developing collaborations and partnership with other BCRF grantees, I have numerous collaborations. I can’t even start counting them with you. Those have been, again, very important for us to advance the science. I will add another benefit, which is the BCRF also supports education and mentorship of a lot of our young faculty members. Throughout the years in partnership with other foundations, such as the American Society of Clinical Oncology, among other many of our trainees received young investigator award or other career development award. Again, BCRF has been instrumental to that. In fact, I was a recipient of the advanced career research award from the BCRF over a decade ago. Again, those have all been instrumental to our continued pursuit in improving all outcomes related to breast cancer.

Chris Riback: Well, thank you for that, and thank you for your collaboration and mentorship and work and research, and for your conversation today.

Dr. Vered Stearns: Thank you very much, Chris.

One key goal in developing precision vaccines and immune therapies is straightforward and imperative: to reduce the risk of breast cancer recurrence. Yet currently, there is only one FDA-approved immunotherapy drug for breast cancer, and it benefits just a small subset of women.

That’s among the reasons that Dr. Karen Anderson is studying the proteins in breast cancers that can be recognized by specialized immune cells, called T cells. These efforts could lead to the creation of vaccines and additional targeted therapies that treat a broader range of patients.

And of course, we’d all like to know: What’s the progress? And how has COVID-19 impacted this progress?

Dr. Anderson, a BCRF investigator since 2015, is a translational researcher at the Biodesign Institute at Arizona State University. She also works as a breast cancer medical oncologist at Mayo Clinic Arizona. Her research focuses on how the immune system can be harnessed to detect and alter cancer development.

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Read the transcript below:

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

Chris Riback: Perhaps we could start with a brief coronavirus update [for] breast cancer patients and their families. What are you hearing from the breast cancer community? What are you hearing from patients?

Dr. Karen Anderson: Oh, it is so important to our patients right now. In the time of coronavirus, it has really changed how clinics are working. It impacts everything that they’re going through. As you know, cancer patients in particular, patients that are undergoing active chemotherapy and immune suppressive therapy are at particular and potential for risk because they’re immune suppressed. And it is so important and challenging for them to actively undergo care, to work out the logistics of going into the clinic, how to get tested, how to isolate effectively.

Dr. Karen Anderson: Also, in how we deliver care obviously, there’s been a lot more rapid and necessary development in videoconferencing, in tele-health and tele-medicine and trying to limit contacts and exposures for our patients so that we can focus on the care that they need.

Dr. Karen Anderson: It’s been incredible how the community has come around to help facilitate the care of our patients and being able to provide cancer care and top-flight cancer care in this time. And help protect them as well during coronavirus.

Chris Riback: We are already in a high-stress level of the situation. It seems like it’s just another real degree of difficulty.

Dr. Karen Anderson: Oh, absolutely. They have enough to worry about but I will tell you, my patients are extraordinary with their families taking this in stride. They’ve just made the adjustments that they need to do. And clinically, also with adjusting prior to chemotherapies, with adjusting treatment regimens and being able to really take it in stride and move forward with it.

Dr. Karen Anderson: I mean all of us know people who have been dealing with it. It changes the way that we’re able to communicate with people. It’s tough on our patients. There’s no question.

Chris Riback: Now, you work at Arizona State Biodesign Institute. I understand you do your clinical work at the Mayo Clinic in Arizona but in reading and researching for this, I saw where the Biodesign Institute has been converted into a fully FDA-approved and clinically certified lab capable of performing thousands of COVID-19 tests per day. Have you been involved in that at all?

Dr. Karen Anderson: Well, when coronavirus was starting in our community, it was recognized by the leadership in our institution that we were going to need to be able to do more testing. We had the fortune really to have high-throughput robotic systems that were capable of doing these kinds of tests, not for COVID-19 specifically, but those types of quantitative PCR tests already here for really another project. And so that work was pivoted over to developing a sort of a high-level clinical lab type of a setting for coronavirus.

Dr. Karen Anderson: Several of the members of my laboratory have been working in the corona viral testing facility, including my lab manager. We’ve been able to shift some of the work so that they can ramp up and be able to do this testing. It’s been really important for the university and for Arizona to be able to provide more testing facilities and capabilities for identification of people, to be able to screen people and emergency workers as well, and to start thinking about what it’s going to take to return, and the return to work components of this.

Dr. Karen Anderson: So, they were able to ramp up for testing and I think that that’s been critical here at the university. And we’re just now starting from a laboratory standpoint to think about reopening laboratories for other types of research.

Chris Riback: Talk about translational medicine and taking learnings from one area of science and applying them to others. I’ve heard that part of cancer research so much. And you’re just describing a whole other level of that kind of taking of skills from one part of science and applying them to another. And it just sounds like all hands on deck.

Dr. Karen Anderson: Absolutely, but I think that there have been a lot of advances in nucleic acid sensing and testing that is coming out from the COVID-19 epidemic that I predict and in turn, will end up impacting breast cancer diagnostics and care as we learn better how to sense nucleic acid in this case for corona viral nucleic acid. But I think that many of those systems and approaches are going to start to be applicable for other things, whether it’s in infectious diseases for our patients or whether it’s actually genotyping identification of high-risk individuals processes like that. I suspect there’s going to be a collateral benefit, I would say.

Chris Riback: Well, that would be fascinating. It’d be kind of nice for something positive like that to come out of this challenge that everyone is facing. If we could, let’s talk a little bit about your work. And broadly speaking, you are in the vaccine business and we hear a lot about vaccines these days, of course, with the search for the coronavirus vaccine.

Chris Riback: At the highest level, now that many of us are getting kind of a 101 on how to create a vaccine from people like Dr. Anthony Fauci. How does your process compare to what we all hear about on television nearly every day?

Dr. Karen Anderson: What we do in our laboratory has been identifying neoantigens or neoepitopes. And what that means is trying to find out what’s different about the cancer cell compared to a healthy cell and use that for the vaccine.

Dr. Karen Anderson: So, in coronavirus, it’s relatively straightforward. The virus is different and so you can take pieces of the virus and then you can generate vaccines to those pieces of the virus. And most vaccines that are being developed for coronavirus are trying to target antibody immunity, just like most of your usual vaccines for pathogens and infectious disease. But for cancer, the types of vaccines that we’re looking at developing are really designed to create T cell responses. It’s the other sort of half of the immune system and how it will react against cancer.

Dr. Karen Anderson: So we’re trying to create strong T cell responses but they have to be specific to the cancer and not to healthy tissue. And so a lot of what we try to develop is what is different about a cancer compared to a healthy person. And it’s different for everybody’s breast cancer. They mutate and they alter in different ways. And so, you have to do it in the context of those tumors.

Dr. Karen Anderson: So what we’re doing is trying to identify what those targets are for each individual person. And then to think about how to design those next generation vaccines. Along the similar kinds of lines that people are doing for coronavirus, there’s a lot that overlaps in strategy. And then eventually try to get those into clinical trials.

Chris Riback: It’s a very different process that you’re undergoing than what we all might be becoming used to and hearing about every day. Is that correct?

Dr. Karen Anderson: Yes. I mean it’s the types of targets and how to build them are much more complicated because you’re not just looking at a spike protein or a piece of the virus. You have to go after the tiny little pieces that the T cells see and they’re much smaller little fragments. And you got to kind of rebuild them into a new version of a vaccine. It’s like putting a bunch of a little jigsaw puzzle pieces back together.

Chris Riback: Your research is described as focusing on how the immune system can be harnessed to detect and alter cancer development. I love that description. What does it mean to harness one’s immune system?

Dr. Karen Anderson: Well, I think what the field of cancer immunology has realized over the last decade is that for a lot of cancers in particular in breast cancer, triple-negative breast cancer and HER2 breast cancers have pre-existing immune responses. So, it’s not that the immune system hasn’t been involved and it doesn’t already recognize that cancer, but the cancer turns it off.

Dr. Karen Anderson: And so, part of what your main therapy does is just reactivate what’s already there. And then part of what vaccines are designed to do is to try to retrain it to recognize even more strongly and more robustly. But what we have learned is that across the board in cancers, whether it’s lung cancer or bladder cancer or breast cancer, a lot of these cancers have some amount of what we call pre-existing immunity and they’re what we call hot tumors. In other words, there’s an inflammation that is already occurring at the cancer and part of the strategy is just to wake that back up.

Dr. Karen Anderson: And then there’s a subset of breast cancers that are cold, that don’t have a lot of pre-existing immune response. And there you really have to get it reactivated. You have to try to drive it to new responses and try to make them more immune active.

Chris Riback: And what’s the why? Why are some hot and some cold? Why do you need to reactivate? Why is the reactivation process so challenging? Talk to me about the discovery process that someone like you has to go through.

Dr. Karen Anderson: Yes, it’s a great question. I’m not sure that we know why some are hot and some are cold. What we do know is that the more mutated, the more altered that tumor is, the more sensitive it is for immune therapy. So in other words, the immune system has more things it can see that are different. You’re looking for differences between tumor and normal tissue, the more changed that tumor is, the more things we can see as different. And that is certainly related in part to a tumor being hot versus cold is how different is it. And then it’s also in part how the tumor itself has evolved to evade the immune system. It does it in different ways.

Dr. Karen Anderson: And so scientists like myself are trying to look at what are the different ways because I suspect we’re going to be designing vaccines that are going to be different depending on how those tumors are immune silenced, how they’re evaded the immune system, how they’re cloaked really from the immune system. And that’s going to be different for different types of breast cancers.

Chris Riback: Yes and the good news in your work as I understand it is that targeted immunotherapy with checkpoint inhibitors has been effective in some patients with solid tumors, including triple-negative breast cancer. The challenging aspect, of course, is that only a subset of patients respond. Is that accurate? Is that the status of some of the work to this point?

Dr. Karen Anderson: Absolutely. We now have the FDA approval of Sacituzumab chemotherapy for women with stage four breast cancers. It clearly has a benefit in a subset of patients and it’s those tumors that rely on that PPD-1/PD-L1 pathway to turn off the immune system. So that was really the first evidence that a sort of a T cell-targeted type of approach can have an impact for patients with breast cancer. But that’s only a subset of women with triple-negative breast cancers. So what about the rest? And how can we make that work better?

Dr. Karen Anderson: So, some of the work obviously that a lot of people are doing and trying to identify, which cancers are going to be sensitive to immune therapies with the ones that we already have available. And then the next step is what new immune therapies can we use for breast cancer to try to make them be seen by the immune system, to turn those cold tumors hot, to try to create vaccines that might reduce recurrence rate, which is really what we’re focusing on.

Chris Riback: In terms of your focus, you use as I understand it computational programs as well as proteomics.

Chris Riback: The large-scale study of proteins made throughout the body. How do those approaches work together?

Dr. Karen Anderson: So, we rely on computational systems to help us see what is different between the tumor and normal breast tissue. And what we’ve been looking at up until this past year has been well what’s mutated. One thing is mutated. One thing isn’t. Is there something in those mutations that we might be able to see? Like mutations and genes like PIK3CA or P53, driver mutations that are found throughout breast cancer. So unfortunately, that’s only a small subset of the differences that are in tumors between healthy and tumor. And so we’ve started to develop new or broader scale prediction programs to be able to mine the huge amount of differences that are hidden.

Dr. Karen Anderson: And I would say that the mutations are just sort of the tip of the iceberg of about what is different in a tumor versus normal tissue. And so, we’ve now developed some newer computational programs to look at the broad array of genes that are expressed, are unique, and it might be highly immunogenic.

Dr. Karen Anderson: A new one that we just developed recently looks is a program called Ensembl MHC. And what that does is it helps improve our prediction efficiency. So, we combine proteomics and what proteomics is, is it’s a broad study of all the proteins in the cell.

Chris Riback: Are the computational programs, the work that your colleagues are adding to the proteomics and to the ability to kind of analyze or make predictions about thousands of proteins at a given time? Is that computational work almost reinventing the approach?

Dr. Karen Anderson: It’s been changing my mindset. And if you think about targets that you can drive an immune response to; and if you think well maybe there’s a couple of targets in that tumor, you build your vaccines in one way. You approach it in another way. If this combination of computational systems and proteomics tells you, “All right, there’s actually these 250 targets.” Then it might be very good and there might be another thousand underneath that, that might be there but maybe it changes the way we do science. It changes the way we prioritize these. It changes the way we think about our vaccine strategy, about what we might need to do to create an effective immune response because the one thing we know about cancer is it’s very good at changing.

Dr. Karen Anderson: It’ll mutate, it’ll alter. If we create a vaccine to one thing, it’s going to try to lose that thing. It’s going to change it. It’s going to mutate it. It’s going to evolve some other cancer that maybe doesn’t rely on that. It’ll find ways around that immune response. So, you need to target multiple things. You need to go after multiple targets and you need to do it early. And you need to do it effectively early on. That’s the best way to reduce recurrence of cancers.

Dr. Karen Anderson: We know this. We’ve learned this from chemotherapies and from hormone therapies and others.

Chris Riback: Is it accurate to describe one of your goals is to determine what proteins and breast cancers can be recognized by the T cells of the immune system? Is that an accurate characterization of one of your goals?

Dr. Karen Anderson: Yes, absolutely.

Chris Riback: Okay. So then here’s my dumb question to follow up on the goal. For all of us, would our T cells recognize different proteins?

Chris Riback: Okay, for patient A, which proteins do his or her T cells actually recognize?

Dr. Karen Anderson: I think that as with all things, it’s a combination. There are common targets that the immune system can see, something like HER2/neu is a common target for 25 percent of breast cancers. But what we’re going after is actually going to lead to more precision medicine. It’s going to be different for every single tumor because we know that they mutate and they alter differently. And the immune system and how T cells see things is you have different HLA. You have different genetics on how your immune system sees a tumor or sees a virus or sees a coronavirus on how your immune system sees it compared to somebody else.

Dr. Karen Anderson: And that’s based a lot on your genetics. And in the same way that that your transplantation proteins, you can’t just transplant a kidney from one person to another. It needs to be a match. It’s the same kind of idea. So we have the tumors that are unique and then your immune system that’s unique. And so both of those lead to what will probably end up being precision based immune therapies.

Dr. Karen Anderson: Now there are a lot of people, ourselves included, who are trying to find some parts of that, that are in common between people. So we can start with the simpler ones that are in common. And like PIK3CA mutations or P53 mutations where you’ve got common targets that might be present in 2 percent of breast cancer patients or some number. And those might be a place to start but I think ultimately, I predict we’re going to have to have precision vaccines that are unique for each individual patient.

Chris Riback: What are you most excited about regarding your work right now?

Dr. Karen Anderson: I am most excited right now with when we integrate the proteomic work, when we integrate that type of biochemistry with the power of computational structure work. Then I think what we can start to do is to bypass a lot of the really slow biochemical work that gets us there. And what am I trying to explain? So let’s say your tumor has 100 or 1,000 targets. Okay, I can go test those in the laboratory but it’s very hard to design a vaccine with a thousand targets. Maybe we can do it to 100 or something but we need to know which hundred we want to go after, which 50 we want to go after.

Dr. Karen Anderson: So, to narrow that down has actually been hard and we’re starting to develop structure-based modeling systems to be able to tell us, “Well, these are ones we really need to go after.” And so we can speed up the process because for me, taking months in the laboratory to narrow that down, we’re now learning, “Okay, well maybe this computer can tell me which 50 to go after and it only has to run an hour to be able to tell me that.” And the better we get at that, the more efficient we get at this, then we can really start the efficiency of trying to design the best possible vaccines to reduce your current rates. And do that in a timely fashion and efficient fashion, that’ll make it feasible to manufacture these things, and to be able to deliver them.

Chris Riback: And it’s so straightforward to understand how that can directly impact people’s lives and quality of life. And we started out this conversation talking about the amount of stress that a person and her family is under when going through breast cancer, and other diseases and situations as well. But that back-of-the-mind worry about recurrence has got to be ongoing, one of the great stress components. And what you’re talking about, heightening the ability to potentially work on and reduce recurrence and do it in an exponentially faster time, that the line that from your work to potentially improving one’s lifestyle at the least. If not, one’s potential life expectancy that’s got to feel pretty good.

Dr. Karen Anderson: We will see what role things like vaccines have in the armamentarium that we have for cancer care. The more ways we can go at this, the better we can do to reduce recurrence and also reduce toxicity. That we can go at cancer multiple different ways. And I certainly envision a time where part of our adjuvant therapy, maybe you get your surgery, maybe you get your treatment before surgery, maybe you get radiation. But part of this is also going to be immune therapy to reduce recurrence, immune therapy of some form.

Dr. Karen Anderson: And I am hopeful that that will start to have an effect and a benefit for patients with cancer. I think that remains to be seen. There are a lot of clinical trials ongoing right now already with vaccines, targeting for triple-negative breast cancers for HER2 type vaccines for others but I think you’re going to start to see a lot more of those clinical trials coming forward as we learn who might benefit from them and which one’s work and which ones don’t.

Chris Riback: And as we talk about those clinical trials and to start to close out our conversation, what role has BCRF played in your research?

Dr. Karen Anderson: They’ve been absolutely integral for everything that we’ve been doing for the vaccine development. They have funded some of the very early research that we need, the pilot research, sometimes the crazy research where it’s early and it’s developmental. And you have to do that in order to get it to a point where you can compete for regular grants or do other projects. And it has really allowed me and my laboratory to do a lot of focus on breast cancer, and on this particular question in breast cancer.

Dr. Karen Anderson: I think BCRF is an incredible organization. It allows us to come together as researchers and as clinicians. We talk about our work. We collaborate. We have one mission and one mission only and to prevent and treat and help our patients with breast cancer. And that guides everything that we do on this project and BCRF reminds us of that. The support is absolutely undeniable in terms of the impact it has on the breast cancer community, breast cancer care.

Chris Riback: Dr. Anderson, thank you. It’s always a treat to get to talk with you. Thank you for the work that you do and thank you for taking the time with me today.

Dr. Karen Anderson: Well, thank you so much. This has been great, Chris. Thank you.

Most breast cancers are not the result of inherited mutation in cancer causing genes. For families with a high incidence of breast cancer, however, a genetic component may underlie an inherited risk. We know the BRCA genes are the most common of these inherited mutations, but scientists have uncovered many more genes implicated in a risk of breast cancer.

How can researchers provide more precise risk estimates so that individuals with inherited risks can make informed decisions about their health, so that the right women are getting the right tests at the right age?

Dr. Robson is conducting studies that employ advanced technologies that incorporate information from genetic tests to enhance the precision of genetic risk assessment in women with mutations in the BRCA gene.

Dr. Robson has been a BCRF investigator since 2006 and is an associate attending physician of Clinical Genetics and Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center.

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Read the transcript below:

Intro: Most breast cancers are not the result of inherited mutation in cancer causing genes. For families with a high incidence of breast cancer, however, a genetic component may underlie an inherited risk. We know the BRCA genes are the most common of these inherited mutations, but scientists have uncovered many more genes implicated in a risk of breast cancer.

So how do genes influence breast cancer risk? And can we develop strategies to precisely predict risk on an individual level? In other words, how can researchers provide more precise risk estimates so that individuals with inherited risks can make informed decisions about their health, determining the level of risk for enhanced screening so that the right women are getting the risk tests at the right age?

Dr. Mark Robson is one to ask. With Dr. Kenneth Offit, Dr. Robson – among other activities – is conducting studies that employ advanced technologies that incorporate information from genetic tests to enhance the precision of genetic risk assessment in women with mutations in the BRCA gene.

Why does he do it? What motivates him? You’ll want to hear Dr. Robson’s thoughtful response about the breast cancer community that included references to James Madison, Virgil, and the that that, as Dr. Robson says: “Life is full of nuances,” and that “everyone experiences” the disease “in a different way.”

Some background: Dr. Robson is an Associate Attending Physician of the Clinical Genetics and Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. He is currently the Clinic Director of the Clinical Genetics Service and the chair of the Cancer Genetics Subcommittee of the American Society of Clinical Oncology. He has been a BCRF Investigator since 2006.

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

Dr. Mark Robson: Thank you for having me. Glad to be here.

Chris Riback: I’d like to start with your helping differentiate between two paths to breast cancer, those that result from inherited mutation and cancer causing genes and those that don’t. Do the types of breast cancers that result from these paths differ and which path is more common?

Dr. Mark Robson: Yes. So, the vast majority of breast cancer is not due to mutations or the term now is pathogenic variants, which is a little bit more fancy but precise. The vast majority of breast cancer is not caused by those genetic changes. They arise because of alterations that occur in the DNA and it’s just acquired through life. But there are a fraction of women who develop breast cancer because of a specific inherited mutation.

And they’re in general have the same outcomes as women who don’t have mutations. And with one exception, the breast cancer is generally seem to resemble those of women who don’t have mutations. The one exception is for women who have mutations in BRCA 1, which is linked to an increased risk of a triple negative breast cancer, which is a particular subtype.

The reasons for looking for these mutations are that … There’s a couple of different ones. One is that women who have mutations, for instance in BRCA 1 or BRCA 2 may be an increased risk for other types of cancer, either second breast cancers in the other breast or ovarian cancer. And that risk means that we should do different things to follow them up.

Also, their family members may be at increased risk if they share the mutation and benefit from specific surveillance approaches and potentially even preventive surgeries. And lastly, women who have metastatic breast cancer with mutations in some genes, although not all genes may benefit from treatment with a specific class of drugs called PARP inhibitors.

Chris Riback: And that’s what I just wanted to ask you about. When we talk about inherited risk or pathogenic variants perhaps and genes and breast cancer, most often we hear about what you just raised, BRCA 1 and 2. But those aren’t the only genes implicated in a risk of breast cancer, are they?

Dr. Mark Robson: No. Indeed not. When a new type of technology called next generation sequencing became available a number of years ago, it became possible to test individuals for many different genes at the same time. And once that became possible, so-called panel testing came into the clinic.

And we discovered that a significant number of women have pathogenic variants or mutations in genes other than BRCA 1 and BRCA 2. And while BRCA 1 and BRCA 2 are still the most common identified inherited risk factors, there are a range of others that in aggregate are equally calm.

Chris Riback: There was a quote I saw recently from Larry Norton of Memorial Sloan Kettering, but also obviously BCRF, where he said, “We know from our data at Memorial Sloan Kettering that if you only test people with strong family histories, you miss half the cases.” And I know this is a key question. If we know inherited risk is a thing but we don’t necessarily know which genes drive the risk, how can individuals with inherited risks make informed decisions about their health?

Dr. Mark Robson: Well, I think that that’s a topic that we’re having a lot of discussions about right now. So, I think what Larry was referring to was that even among women who have BRCA 1 and BRCA 2 mutations… Sorry about the phone. Even among women who have BRCA 1 and BRCA 2 mutations, half of the women with mutations aren’t found until they themselves develop a cancer and would not have been tested based upon what their family history is until they themselves develop a cancer.

That’s one component of the unidentified risk. The other component is that the genes other than BRCA 1 and BRCA 2 are actually much less strongly predisposing than BRCA 1 and BRCA 2. So, they may move through families without actually causing cancer. And so, can be hidden, if you will, until perhaps someone is unlucky enough to develop the disease and get tested.

Chris Riback: Let’s talk about your work and some of your goals. Because among your goals, as I understand it, is to determine not only how we can make more precise risk estimates but how we can precisely predict risk on an individual level. Take me through that process. How are you trying to do that? And perhaps relatedly, what are single-nucleotide polymorphisms?

Dr. Mark Robson: Right. Should we call SNPs because there’s so much easier to say?

Chris Riback: Thank you. We will call them SNPs.

Dr. Mark Robson: Yes. SNPs. So, what we’ve been talking about so far are so-called rare variants. In other words, everybody has the BRCA 1 or BRCA 2 gene but very… Because they perform normal functions in our bodies. But very, very few people actually have mutations or pathogenic variants in those genes. In the general population, it’s probably only around one in 400, maybe one in 500 people have a mutation. Although in certain populations that we’ll talk about later, it may be more common.

These rare variants are predisposed to cancer but not everybody who has a mutation in one of these genes gets cancer. So, for instance, for BRCA 1, it’s probably about 65 to 75% of women get breast cancer and 40 to 60% get ovarian cancer depending on the study. For BRCA 2, the numbers are perhaps a little bit lower. It’s maybe two thirds get cancer and 15% or so get ovarian cancer.

And for genes like those other so-called moderate penetrance genes, those other genes that we talked about a little bit earlier, one such gene is called CHEK2. And for those women, the lifetime risk of breast cancer is maybe about 25%. So, the question becomes what’s different about the women who do get breast cancer and don’t get breast cancer when they have a mutation in one of those genes? And there’s a number of things that play into that.

But one thing is genetic background. And we have millions and millions of places throughout our DNA where we’re subtly different from other people. These are so called common variants or SNPs. And it turns out that some of those SNPs are associated with greater or lesser risks of disease. And this isn’t just breast cancer, this is all kinds of diseases, diabetes, cardiovascular disease, et cetera, et cetera.

And they’re not mutations in the sense that they don’t cause problems with genes but they’re just part of us, part of our background. And we can now through genetic testing in research settings, identify the pattern of common variation that a person has. And what we found is that certain patterns of common variation, so-called polygenic risk scores are associated with greater or lesser risks of disease both in the general population and in people who have mutations in genes like BRCA 1, BRCA 2 or CHEK2.

So, one of the things that we’re trying to do is measure this background variation in individuals, predict how that might affect the risk that’s associated with say a mutation in BRCA 1 or BRCA 2 and see whether if we give that information to women, the differences are sufficient to influence their decision making about things like preventative surgery.

Chris Riback: Almost focusing the light on the amount of risk based much more on an individual reading it seems than on the readings that we have had to date.

Dr. Mark Robson: Correct. Because right now when a woman goes in for a genetic counseling, for a BRCA mutation, she is often given a fairly wide range of potential risks. Say, “Your risk may be anywhere from 65 to 95%.” And what we’re exploring is whether it is helpful to those individuals to become a little bit more precise. There’s still going to be some range but the question is can we narrow that range in a way that it’s helpful?

And it may be that for the very strongly predisposing genes, the precision may be helpful. We may narrow the range but the range may still be so high that it doesn’t change decision making. But for this other group of genes that we have been talking about, the moderate penetrance genes, it may matter.

Because if your average risk is 25 to 30% but there’s some group of women that are in the 15% range and some group of women that are in the 40% range, that may well have an influence on what they decide to do. So, we’re also as a next step looking at polygenic modification of moderate penetrance.

Chris Riback: And is this the Prospective Registry Of Multiplex Testing, PROMPT? So, we had SNP earlier and now we have PROMPT. First, is this the group that you are doing this work with? And then two, how would you characterize where you are on the work? How far along would you say you are?

Dr. Mark Robson: So, PROMPT is actually a little different. PROMPT is when multigene panel testing became available, it is the thing about which we have very little evidence to understand how people are receiving the information, how the information is being communicated to them and what they are choosing to do with the information.

This was something that multigene panel testing was rolled out commercially, not as a research test, with very broad adoption very quickly but with still a lot of questions about how best to use the information. So, we created PROMPT as a voluntary internet based registry for people who had been found to have mutations on multigene panel testing to share their experiences, to tell us what they had because that in and of itself was something that was interesting. What were the diseases that they had, et cetera.

But also, what were they doing subsequently in terms of screening or surgery? And what was their understanding of these alterations? What had they been told? What had they received? And now, we’re following these… Largely women, not exclusively but largely women serially over time to try to understand longitudinally what they’re doing.

So, that’s an observational project that I think is very important because it’s giving us a view of what’s happening in the real world with multigene panel testing. With regard to the risk modifier work, we were facing some challenges getting a clear based… Which is a laboratory approved assay done that we could share with people that we had enough confidence would be accurate.

We’ve now circumvented that hurdle through a relationship with a vendor, have achieved the appropriate regulatory approvals and are now moving it into the clinic to start offering the testing to women who have had newly identified BRCA mutations so that we can give them this information and essentially measure what it is that they choose to do with it.

Chris Riback: And the point that you were just making, I’m sure it’s a question that any person would have first of all around genetic testing and understanding one’s own risk and modifying one’s own risk as much as possible. But in particular, individuals at risk of carrying BRCA 1 or 2 mutation, this becomes even more powerful for them.

You wrote in a recent editorial in the journal of the American Medical Association with a colleague, you wrote a little bit about this. And one of your lines was, “Identification of individuals at risk of carrying a BRCA 1 or 2 mutation can be lifesaving and should be a part of routine medical care.”

Now, that may have been geared towards a particular population but I thought that might be something to get some guidance on or some insight on from you because it’s an area obviously that so many people would be curious about.

Dr. Mark Robson: Right. So, we have reasonably strong observational evidence. That if you identify a woman who’s having a BRCA mutation and then prevent her from getting ovarian cancer by doing a preventive surgery to remove her fallopian tubes and ovaries, that that will improve the survival of the population because screening for ovarian cancer is inadequate and it’s a tough disease that frequently presents an advanced stage.

There is also some potential benefit from women who choose to undergo preventive mastectomy, although whether that has much of a survival advantage is not clear. But prophylactic oophorectomy is something that we believe does save lives. So, finding women who have BRCA mutations, that’s not something that you want to do lightly, certainly not in younger women because premature menopause is quite a significant impairment to quality of life and potentially to longterm health.

Dr. Mark Robson: So, finding the women who’ve got mutations is important. The way that we have done that to this point has been by using things like family history to try to predict who is more likely to have a mutation. Remember as I said earlier, it’s only about one in 400 to one in 500 in the general population. So, creating a system of testing, everybody becomes challenging.

The thought is perhaps to start this process by concentrating on groups who have higher risks of carrying a mutation. So, for instance, the population of the Ashkenazi Jewish individuals. So, individuals of Eastern or Central European Jewish descent have about a one in 40 chance of carrying one of three specific BRCA 1 or BRCA 2 mutations.

So, nearly 10 times higher. And there has been thought now that perhaps everyone who is of Ashkenazi Jewish descent… And defining that becomes a little bit of an issue. But everybody who’s of Ashkenazi Jewish descent should at least be offered or have a discussion about the possibility of undergoing BRCA testing, at least for those three common mutations.

Chris Riback: So, it’s a bit of a shifting of the thinking around who might want to do it. And I’m sure that there’s still much discussion and increasing the number of the amount of testing carries… “controversy” is the wrong word, but one wants to manage – and you were saying this – and handle testing appropriately.

As I’m talking to you, so much of it seems what you think about, what you have worked on in your career, what you’ve dedicated yourself to is around the genetic component and about the considering and the managing of risk. I found myself thinking about you almost as a medical actuary doing, thinking… So, why? What interests you about that? And have you ever thought of yourself as a bit of a medical actuary?

Dr. Mark Robson: No. I never thought of myself as a medical actuary. Because why am I interested in it? That’s a fascinating question that I’ve really never deeply thought about. My perception is that life is full of nuance. And what I enjoy about this area is trying to communicate with people about uncertainty and help them navigate that in a way that is concordant with their values and how they want to approach managing potential threats to their health.

I mean, not everybody who has a BRCA mutation gets cancer. And certainly, not everybody with a moderate penetrance mutation gets cancer. And yet when they have a test result, many people seem to internalize that as a diagnosis, essentially pre-cancer. And the question is how can we help them navigate that and just recognize that this is something that is a risk that you know about. Perhaps there are others that you don’t. And that’s what I enjoy about it.

Chris Riback: And does that lead in some way to your clinical work? I mean, it wasn’t lost on me that my understanding of the clinical side for you, you’ll correct me if I have this wrong, is that your practices weighted toward the management of young women with breast cancer, especially hereditary breast cancer. I recently had a discussion with Doctor Ann Partridge, who runs the young and strong program for young women with breast cancer. The disease is different for young women, isn’t it?

Dr. Mark Robson: I think that the disease is different for everybody, right?

Chris Riback: Yes.

Dr. Mark Robson: I mean, everybody experiences it in a different way and it has a different impact. I do work a lot with younger women just because I work a lot with inherited risk and that overlaps. But also take care of people who are older as well. And it’s the same concept. I mean, if you think about after a diagnosis and treatment of breast cancer, once again, people are living with a pretty fair degree of uncertainty.

About at least for a while, “Is this going to come back? How am I going to integrate this into my life? ” And again, it becomes a conversation about moving forward in the face of uncertainty. And uncertainty with a possibility of something not good happening, right? And I think that from the humanist perspective of Madison that being a little bit of a Virgil in that setting, is a privilege. And I enjoy doing that.

Chris Riback: Was it always medicine for you? Was science always the direction that you were going to go? You mentioned Virgil. Were there other areas of interest for you growing up?

Dr. Mark Robson: I’ve always been interested in the arts and humanities. But mainly as a way of, again, informing perspectives on life. Gosh, I’m getting all philosophical here on a Thursday afternoon. But no. I mean, I’ve been joking with my daughter who’s now in 10th grade and I remember actually starting thinking about doing medicine when I was in 10th grade biology class.

So, yes. I mean, it pretty much has always been medicine for me but for different reasons. When I was younger, it was because it was tough and it was hard and I felt like it was intellectually challenging, which has a certain arrogance to it. And then, as I got older, it became much more because it was a life of connection. And connection not only to your patients but connection to your colleagues and connection to the broader world. And I think that’s a very nourishing thing.

Chris Riback: Yes. It’s not a bad way to go through. And to close out, I’d be remiss if I didn’t ask you, doing the amounts of research that you do and that other researchers, scientists, doctors do can be challenging at times, what role has BCRF played in your research?

Dr. Mark Robson: Well, BCRF has been an incredible financial supporter. The model is very unique. And the idea that you have funding to explore ideas that would be difficult to get funded through other mechanisms because of the novelty, because of the newness of what you’re trying to do. So, there’s that component to it.

The other component goes back to what we were just talking about is that it’s a phenomenal community of both researchers but also… And perhaps more importantly, patients, family members, supporters, who are energizing through their dedication to the course and their energy for the course.

And so, I think we all talk about the research support that’s critically important. But the community writ large is in my mind equally important and perhaps even more so.

Chris Riback: Well, thank you. I’m certain that they’re grateful to have you part of that community. And yes, it’s a remarkable community to say the least. Dr Robson, thank you for taking the time. And of course, thank you for the work that you do.

Dr. Mark Robson: Thanks very much. Appreciate it.

Every October, BCRF-funded researchers are honored at the annual Symposium & Awards Luncheon in New York City. This is when BCRF makes its formal announcement of research grants for the upcoming year and recognizes its investigators for their devotion to ending breast cancer with their trailblazing scientific inquiry. The event provides a unique opportunity for BCRF researchers to convene, share ideas and collaborate with fellow colleagues from around the world. This year’s program began with a symposium featuring an expert panel of BCRF investigators. They discussed current breaking topics in breast cancer research, ranging from prevention and diagnosis to treatment and survivorship. We’re proud to share that discussion here in this special bonus podcast.

Subscribe to Investigating Breast Cancer here:

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Read the transcript below:

Intro:   I’m Chris Riback. This is a special bonus episode of 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.

Each October, BCRF-funded investigators are honored at the annual Symposium & Awards Luncheon in New York City. The event announces the Foundation’s grant investment for the coming year and recognizes BCRF investigators— many of whom we feature in these Investigating Breast Cancer conversations — for their devotion to ending breast cancer and their trailblazing scientific inquiry. The audience is comprised of researchers and BCRF supporters, and the gathering provides the rare and unique opportunity each year for BCRF researchers to be in one place to share ideas and collaborate with fellow colleagues from around the world.

This year, the program began with an extraordinary symposium. An expert panel of BCRF investigators discussed current breaking topics in breast cancer research, ranging from prevention and diagnosis to treatment and survivorship.

We’re proud to bring you that discussion here, in this special bonus podcast. The symposium panelists included:

• Dr. Eric Winer, of Dana-Farber Cancer Institute. Dr. Winer is also the recipient of BCRF’s 2019 Jill Rose Award for Scientific Excellence.
• Dr. Dawn Hershman of Columbia University Medical Center.
• Dr. Neil Iyengar of Memorial Sloan Kettering Cancer Center.
• Dr. Judy Garber, of Dana-Farber Cancer Institute. Dr. Garber also serves as BCRF Scientific Director.

The panel was moderated by BCRF’s Founding Scientific Director Dr. Larry Norton of Memorial Sloan Kettering Cancer Center.

We’ll have our regular episode of Investigating Breast Cancer in the next weeks. Now, here is Dr. Larry Norton and BCRF’s 2019 Symposium.

Dr. Larry Norton: Welcome everybody. I don’t know how many years we’ve been doing this, but every year it gets better and better. And thank you all for being here. Other people will be coming in as the usual thing over this next hour or hour and 15 minutes that we’re doing this.

We changed the format just a little tiny bit and we’ve asked this extraordinary group of grantees, clinician scientists to be educational in their focus as well as talking about their own research, but also to educate on very important topics.

And I’m going to pass the podium on to the group so as not to waste time as a nascent to introduce themselves as Dawn Hershman, Eric Winer, Neil Iyengar and of course, Judy Garber, who’s the scientific director of the BCRF to introduce themselves and we will talk about their topics a little bit more depth than we’ve done in the past.

Before we get started, I’ve introduced my colleagues here. I just want to introduce one other person because it’s an exceptional few weeks is Bill Kaelin, one of our grantees from 2006 just won the Nobel Prize. Bill.

Okay. Thank you. Very gratified by your work, extraordinary and huge impact. And I expect all the other grantees who are sitting on both sides and may have comments as we go forward. Every year I want one of you to win a Nobel Prize. All right. It’s extremely important that we do that because we got to keep the momentum going in this regard.

Okay. Let’s just start off with the main program. And I’d like to introduce Dawn, introduce yourself and tell us about your topic.

Dr. Dawn Hershman: I’m Dawn Hershman, I’m a professor of Medicine and Epidemiology at Columbia University and a breast cancer oncologist. Early in my career, I think one of the things that really stood out to me was the number of people that would really… We’d have all these great treatments for breast cancer even though we have a long way to go, we have some really spectacular treatments.

And it always stood out like that, a large number of people wouldn’t get those treatments. They wouldn’t start those treatments, they wouldn’t finish those treatments, and we spent all of this time, energy and effort trying to discover and put forward new, better ways of treating breast cancer, but not everybody got them.

I remember early on, we started using anti-hormone therapy, anti-estrogen therapy, and patients would come in after we put on aromatase inhibitors in particular, just in tears because the side effects would make them miserable. They would say things like, “I can’t get up from my chair. I can’t go down the stairs in the morning. I know these medicines work, but I can’t take them, I don’t know what I’m going to do.”

And it really made us start to think like, well, how many people are like this out there? How many people can’t take their medication and what are the reasons why? And we started to investigate that and we found that over 50% of patients couldn’t complete the five years of treatment on time the way they were prescribed.

A lot of people stopped, they took it intermittently. So it made us start to think, well, what can we do to try to help fix that problem? And when we first started to go back to the clinical trials, they were why, why is there a discrepancy in terms of what people are saying versus what we see in the clinical trials, in the clinical trials maybe only 8%, 7%, so they had a problem with side effects.

We started to realize that we weren’t really measuring side effects in clinical trials because we weren’t asking patients how they felt. And it really opened our eyes to the importance of asking patients while they’re on treatment, what the side effects are that they’re experiencing so that we can better measure it, we can have appropriate outcomes to know, but also so that we can control those side effects so that we can keep people on their treatments.

So it started a whole way of us thinking about patient-reported outcomes and incorporating that into trials and putting in the patient’s voice so that we know exactly what we’re talking about when we get these results. In thinking about side effects and why people stop taking their medications, we’ve looked at a lot of different things.

We looked at financial factors and how even small differences in the amount of money you have to pay out of pocket can make a big difference in terms of your likelihood of staying on a medicine or the type of insurance you have. But the number one reason why people stop taking their medication is side effects.

So we started to investigate all different types of things in terms of controlling side effects from the aromatase inhibitors and we looked at medications like antidepressants and certain types of medicines like we call Duloxetine or Cymbalta, they can work, but people don’t want to take them because often we hear, “I don’t want to take another medicine that causes side effects to control side effects from a medicine I have to take.”

It’s totally reasonable, so let’s think about other ways we can try to control these side effects. And so we worked with Melinda Irwin who’s a grantee on looking at exercise and can exercise control these side effects? And her study showed that yes, actually exercise can control some of the side effects and hopefully keep patients on their medications.

We looked at other types of compounds like Omega-3 fatty acids to control side effects and that can be effective too in some types of patients, but probably the most impactful thing we did was we studied acupuncture, and we did a very large rigorous multicenter trial looking at whether or not acupuncture could control those side effects.

And people say, “Well, of course acupuncture is going to work because patients would just get it.” But it’s really important to test these things because people pay a lot of money out of pocket and you can have an influence if you find out that it’s actually effective.

What we found was that, we analyzed the data all different types of ways no matter how we analyzed it, acupuncture was better. And what was it better than? Well, we had an arm that was sham acupuncture, so we tried to trick people into a placebo of acupuncture and we had people wait until they got their acupuncture.

The true acupuncture actually was significantly better; it reduced those side effects by more than 50% in terms of improvement. And so if people say, “Well, why do you need to do that?” Well, the reason we need to do it is so that we can convince insurance companies to pay. And the results of those trials enabled us to pressure a fair number of the commercial insurance companies to cover those costs.

And it’s important because we need to think globally and work with every patient in a personalized way to help make sure that whatever the problem is that’s stopping them from getting the treatments that work, that we come up with a solution that’s right for them.

Dr. Larry Norton: Excellent. Thank you so very much. Acupuncture also helps you chair these kinds of meetings by the way. I have a needle in me right now, and if it were not for that.

Eric Winer, who’s the Jill Rose award recipient this year and I have a lot of nice things and some not nice things to say about him a little bit later this morning that you’ll hear. Eric, what’s your topic? Who are you.

Dr. Eric Winer: Who am I? I’m up in Boston and I am a medical oncologist. Oh, sorry, not close enough. Excuse me. I’m at Dana-Farber in Boston where I direct the breast cancer program. I’m a medical oncologist, I do research, I take care of patients. I try to keep everybody happy there, meaning all the people we work with.

You’ll just forgive me if I just tell you a brief story, which is that the fact that I know a lot about breast cancer and very little about everything else was brought home to me many years ago by my oldest son, who at the time was about 11. This is many years ago. And he had a rash on his face, which I kept telling him was because he got chocolate all over his face whenever he ate anything that had chocolate in it.

And he went to the dermatologist, the dermatologist said, “Your father’s wrong. You have perioral dermatitis.” Jeffrey comes home and he says, “Dad,” And he said, “you’re wrong.” I said, “No, Jeffrey, I still think it’s like getting all that chocolate on your face.” He said, “Dad, if I had breast cancer on my face, I’d listened to you, otherwise I’m going to the dermatologist.”

So when your own family feels that way, what can you say? So I asked Judy and Larry what I should talk about and the answer I got was that I should talk about breast cancer treatment and what has happened with breast cancer treatment over the past five, 10, 15, 20 years. And I’ll do this pretty briefly.

Twenty years ago we thought of breast cancer as one monolithic disease. We treated it all about the same. Somebody would come in and say, “What kind of breast cancer do I have?” And I’d say, you have stage one, you have stage two, you have stage three breast cancer.” But in other ways, we didn’t know how to tell one woman’s breast cancer from another.

And the stage tells you how much cancer there is, but it doesn’t tell you anything about the personality of the cancer. And where we have excelled over the last two decades is understanding more about the personality of different cancers or the biologic behavior of those cancers.

And the result is we no longer have one size fits all treatment; we have one size fits all. We have treatments for women who have HER2-positive breast cancer, and women who have estrogen-receptor-positive cancer, and women who have Triple-negative breast cancer. Now in all of these areas, we’re finding out that there are sub diseases within those individual entities, so not all HER2-positive breast cancer is the same.

Certainly, not all triple-negative breast cancer is the same, and for sure the 75% of women who have estrogen-receptor-positive and HER2-negative breast cancer, that’s a very mixed group of tumors and patients who have them. And so we’re doing a lot better.

We’re doing a lot better in terms of having better treatments for many women, and for many others, we’re also learning that we can do as well by them and avoid a lot of these toxicities and side effects that Dawn was talking about by and at sometimes backing off, but backing off in a very thoughtful way so that we’re not putting anyone at risk, but we’re simply trying to give the most effective treatments to the patients who need them.

And for those who may not need such aggressive treatment, we’re learning that in some situations we can carefully do less and there are many people around the country who have taken that approach in terms of trying to figure out which are the patients where we need to develop new drugs and new treatment approaches, and who are the patients where perhaps a little bit less is equally good?

And this isn’t just in medical oncology with drugs. I looked over and saw Laura Esserman sitting someplace here, right there who is as many of you know a surgeon at the University of California at San Francisco and has run a large research program looking at both ways that we can give more and give less medical therapy, but also thinking about the surgical issues and the radiation issues.

Because the whole treatment approach we take sometimes is pretty overwhelming for people. And to the extent that we can be more specific and more tailored to our approaches, we’re going to do better. And I actually think that we’re really getting there. Happy to answer questions about this as time goes on.

Dr. Larry Norton: Thank you. Thank you so much. There’s clear linkage here between the notion. I just want to say editorially is that I’ve seen the whole transformation of the treatment of breast cancer really in my career. I’ve been involved in medical oncology from seven years after the very beginning except for the first seven years, I’ve seen the whole evolution of the field.

And in breast cancer, which has really taken the lead in many respects in terms of moving forward in many ideas. We’ve really reached a point where we can start talking about making the therapies more effective and less toxic simultaneously by choices, appropriate therapy for the right patient by handling side effects of therapy and make sure people take their medications.

And this is really a remarkable thing because you go back 20 years ago, 25 years ago, it was just more and more and more suffer. You got to suffer to get the maximum effect, you got to push people forward in that regard, and that was a very important point in the evolution of the field, extremely important point in the evolution of the field.

Now we’re at another point, which is really extremely gratifying, and we’ll probably have more to talk about as we move forward. And to talk about like feeling really good, I brought Neil Iyengar. All right.

Dr. Neil Iyengar: That’s a great introduction, thank you. Thank you, Larry. I hope I can make everyone feel really good this morning. I’d like to start by saying good morning and it’s my great privilege and honor to be sitting on this esteemed panel and we’re grateful for the support of the BCRF for really accelerating our research program.

My name is Neil Iyengar. I’m a medical oncologist and a clinical investigator at Memorial Sloan Kettering Cancer Center and we focus on how we can optimize our metabolic health for cancer and for improving response to cancer therapies. In other words, preventing resistance to cancer treatment.

So what do I mean when I say metabolic health? Well, I’m talking about factors that we might think about when we go to see a cardiologist or an endocrinologist. Things like diabetes, blood sugar levels, insulin levels, cholesterol, obesity. We know from the work of several BCRF investigators, epidemiologists here today that obesity is a leading modifiable risk factor for the development of several cancers.

At least 13 cancers are related to obesity, and that number will probably grow as we learn more. And if we think about obesity as a classic state of metabolic dysfunction, there’s a lot going on. So we partnered several years ago with the insights of Cliff Hudis who many of you know, with Andy Dannenberg, a BCRF investigator who’s here today as well to collaborate on really understanding the biology of why obesity can promote the growth of breast and other cancers.

If you think about the breast, it is largely composed of fat. Fat is our most metabolically active tissue. And many of you have heard about the concept of the tumor microenvironment. Well, if you look at the tumor microenvironment of breast cancer, one of the most prominent components of that microenvironment are fat cells.

And what we’ve learned is that in the setting of obesity, the fat tissue in the breast and elsewhere can become dysfunctional. Specifically, it can become inflamed and produce inflammatory molecules, which can directly stimulate the growth of cancer cells. In addition to that, those inflammatory molecules can stimulate the production of the enzyme aromatase, which many of you know is the key enzyme for the production of the hormone estrogen.

And so what we’ve found is that this fat tissue dysfunction in the breast can create a tumor microenvironment that is inflamed and pro-estrogenic and ripe for the growth of breast cancer. And this classically happens in the setting of obesity, but beyond obesity, we’ve also found that in up to one third of women who are not classically defined as obese, who have a normal weight, who appear to be healthy and may even be told by their physician that they’re healthy, up to one third of these women also have this fat tissue dysfunction, inflammation, higher levels of aromatase in the breast fat.

And so we’ve learned from the research of several other BCRF investigators here today who’ve pioneered lifestyle interventions for the treatment of side effects, which we heard about from Dawn, that these lifestyle interventions can also improve the metabolic state of the body.

And so now we’re very interested in how we can develop precision lifestyle interventions to help in the prevention and treatment of breast cancer. And what I mean by prevention or precision lifestyle interventions is building on what we heard about from Eric that this concept of one size fits all doesn’t apply not only to our breast cancer treatments, but also to lifestyle interventions.

And so we’re developing personalized exercise prescriptions using BCRF support to leverage technologies like tele-exercise where we’re shipping treadmills out to patient’s homes equipped with tablets such that they can interface through video conferencing with our exercise physiologists here in Manhattan to participate in supervised precision personalized exercise.

We’re developing nutritional interventions, for example, partnering plant-based diet approach with precision exercise for women who are taking aromatase inhibitors to try to improve that health of the breast fat. And finally, if you think about the biology of tumors and how we develop new molecular therapies that are specific to the biology of tumors, we can start to think about that same paradigm for lifestyle interventions like nutrition.

Some tumors are dependent on growth factors or growth pathways that involve insulin. So we’re testing diets that lower insulin, like low carbohydrate or on the other end of the spectrum high protein diets like even the ketogenic diet for supporting the treatment effect of some of our new breast cancer therapies.

And so what I hope I’ve conveyed to you is that one diet or one lifestyle intervention may be right for one person, but may not be the right approach for another person, similar to how we think about our breast cancer therapies. And with that approach, we hope to really develop personalized guidelines, interventions and recommendations for lifestyle interventions that could have an anti-cancer effect.

Dr. Larry Norton: Neil, thank you very much. The general theme is, which we didn’t intend, but is obviously rising is personalization, doing the right thing for the individual. The right way to intervene so that people can actually take medicine they’re supposed to take, the right treatment and the right exercise.

I saw a lot of heads shaking while that was going on. Fill out your questions, all right, please and hand them forward because I think we have a lot to talk about with all of these three topics. But of course the thing that’s most, most specific to you are your genes, and that’s something you can’t escape, the genes you’re born with. Judy, do you have any thoughts about genes and cancer?

Dr. Judy Garber: Is that what you wanted me to talk about? Oh, I’m Judy Garber. I’m a breast oncologist too and I do clinical cancer genetics at the Dana-Farber Cancer Institute in Boston. And I was hoping Neil would have an exercise intervention for the investigators that would help us do it.

Dr. Larry Norton: Oh, no, no, I’m-

Dr. Judy Garber: We’re in a do or not do, we’re in the do side, so personalized would be great. I’ve worked in cancer genetics for a long time. BCRF has been involved in supporting cancer genetics really almost since Mary-Claire King first mapped the first BRCA 1 gene.

And many of us collaborate, which is something else that’s characterized BCRF investigators and breast cancer as a field because we needed to work together to get enough numbers to work. So we’ve known now for many years that breast cancer in particular, but also ovarian cancer could travel in families and be related often to a genetic factor.

And thanks to work by Mary-Claire and many others in this room, we now know about many genes. So we know about BRCA 1 and 2 that are the most common genes, which we’ve been testing now in many women with breast cancer and many with family histories for more than 25 years I think and finding mutations, but we’ve also learned that there are more genes.

And we’ve learned part of that through the work of people like David Livingston, Alan D’Andrea, Alan Ashworth who figured out what BRCA 1 and 2 did, that they’re important in DNA repair, and then mapped down the pathways, looking at all the other genes that were involved to ask, were they also important in breast cancer?

And some of them are, and some to a lesser extent, and some of them contribute to risk of other cancers as well. So for our patients that we tested in the early days and didn’t find anything, who still wonder, could there be something genetic? The answer might be that it’s time to look again now at other genes.

And we’ve learned that our early thinking as is often the case in research, was guided by being strict, as strict as possible to try to have the closest definition so we can at least find these genes and figure out how to use them. So that was what I mean by that is people with the strongest family histories.

But we’ve learned that many people may not have a very strong family history. Through no fault of their own. They may have mostly male relatives in which you don’t see the breast or ovarian cancer, so you’ve had to think about expanding who gets tested and how to make testing more accessible to the broader population of people who may not realize testing is for them.

Now we’ve had to make testing safer, so to work to make the penalties by your insurance companies or otherwise against discrimination against testing. And we’ve had time to do some of that, but now we can concentrate on making testing more available for appropriate populations.

We’re not ready to tell everybody necessarily to be tested, although I don’t think we’re too far from that, at least every cancer patient. So there are studies that are here like the before study, which is for the Ashkenazi Jewish population looking at people who really may not realize at all that they have risks, but just by having even a Jewish grandparent, you may be Jewish enough to have a 10 fold higher chance of carrying a BRCA mutation.

And you may not find it until you’re like the internist I saw on Tuesday who’s had absolutely no family history, but had ovarian cancer. And that’s when she learned that she has a mutation that she inherited from her father and so hadn’t been seen. One in 40 if you’ve heard about them, that’s their story.

We want to prevent this and prevent the deaths from cancer that are avoidable, not only for our breast families, but also now we’ve learned ovary, pancreas, advanced prostate cancer. So the guidelines for testing have expanded so that people with those diagnoses are found.

And part of that is to help prevent cancer in their families, and part of that is because there are treatments now for people whose tumors arise in the setting of a mutation that makes them vulnerable to certain kinds of exploitation by treatment.

So Eric can talk about personalized treatment, this is really personalized treatment. It’s about the way the tumor came to be as much as it’s biology determined by that. So these are the PARP inhibitors. And now there are drugs for people whose tumors become resistant to the PARP inhibitors and can get other drugs to try to restore sensitivity.

Many people in this room are responsible for trials showing that these drugs are effective in advanced disease, now there are studies moving them back to an earlier phase of treatment. And not only treatment, but actually, probably the reason many of us went into this field was to look for prevention strategies, and not necessarily only the prevention strategies that we all find, at least in theory, much more acceptable like diet and exercise, which you know are hard to get people to do.

So we’ll leave that to Neil, but also to other strategies, immune strategies, which are very interesting. Try to get the immune revolution to also benefit prevention, but also drugs that target particular targets. Geoff Lindeman is here and his work has identified a molecule that looks to be important in BRCA 1, breast cancer development.

And now there’s an international study asking, “Can we actually reduce the risk of breast cancer or at least delay it so we can put off those prophylactic mastectomies?” And in that mode, even beyond that, BCRF is investing in prevention, in prevention studies, Novel trials, and Novel approaches this year that we hope will move prevention forward so we can catch up to treatment.

Dr. Larry Norton: Superb. My goodness. The evolution of our field toward knowing much more about the individual so that we can do things that are specific to the individual rather than groups of individuals has really been extraordinary. And I think it’s revolutionary to actually hear it with my colleagues actually presented the notion that it’s not just a matter of what exercise… Go to the gym and exercise is not necessarily good advice, is bad exercise.

You can actually exercise too much, for example, so knowing something about that, knowing about your genes specifically for prevention strategies and moving forward. And I think we’re going to have a lot of discussion of that as we move forward. What is the right therapy so you don’t get stuff that’s going to hurt you and not necessarily help you.

And also, frankly in my mind, leave room for advances that could then be added in. If you clog up treatment to make it too complicated, it’s very hard to back down and very hard to add onto it things that may be useful going off in the future. And ways of handling the complications of therapy in such a way that people can actually adhere to regimens that can help them all depends upon analysis of the individual.

And so it’s the revolution of the individual that we’re hearing about, which is really remarkable. I think it’s partially in my mind just to share with you, it’s advances in science in terms of understanding this, but also I think it’s part of the digital revolution, the idea of enormous amounts of information that can be available and that can help individuals.

We all have enormous access to information that we never had before. I have a smartphone in my pocket, I can get more information out of this than I could have any other time in history and all of us can basically do that. But the idea that information about you as an individual is power for you in terms of your health and the health of your family, I think is all part of this dramatic change really in society, a dramatic change in our way of thinking about ourselves.

Now, you’ll notice I’m not wearing glasses this year because I had my cataracts done, but that also has a downside, which I got to do this all right, which I couldn’t do before. This is a really, I think an overarching question I think for all this, and I’m just going to read the question because I think it’s well worded.

Why do some people still get breast cancer even when they do everything right, healthy weight, diet, exercise, no drinking, family history, et cetera? There’s a philosophical, sociological component of this. Who wants to start that off? Do you have to do something wrong to get breast cancer? Is breast cancer a punishment for something you’ve done wrong? What do you think? Judy, what do you think?

Dr. Judy Garber: No. Unfortunately, we’re not able to explain most breast cancers. We can point to genes sometimes, we can think about lifestyle factors, we can talk about diet and all kinds of unhealthful behaviors, but most of that, but the Metalogic studies show that we can’t attribute a cause for breast cancer.

And I think to some extent it’s chance that our genes are reproducing all the time. Every time your cells turn over, you have to completely reproduce with almost exact fealty, the DNA content of your cells, all your chromosomes. And cells make mistakes and they have DNA repair systems, but as we get older, we make more mistakes, and those mistakes, if they’re in the breast, can go on to be breast cancer.

If the genes are the ones that are responsible for keeping the cells on track, then it’s even easier for cancers to develop. But this is true of all cancers, not just breast cancer, of childhood cancers, we can’t explain those either. So I don’t think that it’s really possible to be organisms without some risk of cancer.

Unfortunately, too often in women, these are cancers, and I would say that I neglected in that to talk about environment because despite decades of very careful study, we’ve done not very well at being able to figure out, which environmental factors we could remove to reduce breast cancer risk. And I do think that there’s something to that.

Dr. Larry Norton: Neil.

Dr. Neil Iyengar: I think I would like to add to that especially in the realm of lifestyle interventions like diet and exercise that we really have to be careful to distance and move away from the notion that it’s something that a person did. Their diet or their exercise for example, that may have given rise to their breast cancer, that’s far from the truth.

And I think that part of that might be how the message is put out there, for example, many of you may have seen the updated guidelines for exercise, for prevention and during cancer treatment published yesterday by The American College of Sports Medicine. The article in the New York Times of course suggests that we may be able to avoid cancer by exercising.

I think that that diminishes the science and the understanding of the complexity of the individual, their genetics, their environment, everything we heard about just now from Judy. And really understanding that individual biology and parent lifestyle interventions that may compliment other prevention strategies or cancer treatment strategies is something that we have to think about with much greater nuance and depth.

Dr. Larry Norton: We could talk about this one topic really forever. There’s always that question, which is a recurring question always reminds me of the opening scene of… There was a book about the beginning of the space program called The Right Stuff and they made a really good movie about it. I think the book is better than the movie actually, even though the movie was really great.

And the opening scene is a bunch of test pilots sitting around because one of their colleagues testing the airplane has just crashed and died. And they all go around saying all the things that that pilot did wrong, “Oh, we know he never checked his fuel, he never checked his gauges, he never got enough sleep.” They were all going round in a circle.

The fact that matters is he’s a test pilot, sometimes planes are going to crash and you could do everything right and they’re going to crash, but there is one other thing you can do in addition to everything we’ve talked about, in addition to understanding that that things can happen to you that are bad even though you’ve done nothing, which is support research. You’re all here to support research.

All the advances we’re talking about just didn’t happen by just random chance, they all happened because of the sport of research, basic research, applied research, clinical trials, survivorship, the whole spectrum, which is represented by my extraordinary colleagues on both sides of this room.

So your supportive research helps you and helps your family, and I just want to point that out as an extremely important component of what you can actually do in addition to all the personal things that you can do that we’ve already mentioned.

I have a question here that I know was going to come up because it was just on the news yesterday and apparently made a whole big fuss, so I’m just going to answer. Is about a breast cancer vaccine that was tested in Moffitt apparently and it was presented in a very short press release as a major, really advanced.

She got a vaccine and her cancer disappeared. It wasn’t breast cancer, it was ductal carcinoma in situ, which is not a cancer. It’s a sign… It’s a bad term because it has the word cancer carcinoma in it, but it’s basically it’s an indicator of the possibility the breast would turn to cancer.

She had a positive biopsy, she got a vaccine, then had re-excision and they didn’t see evidence of DCIS. Sometimes do nothing if you have a positive biopsy and do a re-excision, you’ve got no evidence of DCIS. It needs an enormous amount more study to see whether it’s something that’s a value or not.

And it’s received a lot of… When I got home last night after we had BCRF events last night, I had about 40 emails about, “Why can’t I get this new vaccine?” So really it’s very early on, it’s got to be tested appropriately. It wasn’t a cancer vaccine, it was a vaccine for cancer predisposition. So I just wanted to mention that because we have a bunch of people that have asked about that.

One thing I’d like to ask Eric about is there are a number of questions here about the side effects of chemotherapy. We heard about the side effects of aromatase inhibitors therapy, what’s going on in decreasing the side effects of chemotherapy?

Dr. Eric Winer: It’s a complicated question because there are a number of different things going on. First of course, is trying to give less chemotherapy and doing it… avoiding chemotherapy when we don’t need to give it. And the second I would say is, how we give the therapy. We know that when we combine many drugs together that there are more side effects than giving drugs one at a time.

We know that sometimes it’s better to combine them, but sometimes it isn’t. But in terms of actually reducing the side effects that exist, there’s also a great deal of research that’s going on looking at that and there are many BCRF investigators who have focused their efforts in that area.

We know that treatment of nausea for example, is something that is still a problem, but it’s very different than it was 20 years ago. I think one of the most challenging side effects that we see is actually neuropathy, which can both be an acute problem and a chronic problem, and so needs a great deal of study.

But that’s another one where I think that much of what we need to do is pay close attention to the patient and be careful to back off on the therapy when the side effects are beginning to get to be perhaps worse than any other problem. I think it’s something that when a patient is seeing a doctor, there’s often a focus on treating the cancer and not so much paying attention to the side effects.

And sometimes patients don’t want to waste time and the appointment to talk about side effects as much as they want to talk about where they’re going with their cancer treatment. And I just remind everyone that it’s really something that has to be part of medical conversations all the time because the one thing we don’t want to do is treat someone effectively and then leave them seriously debilitated with side effects, and that does happen occasionally less than it ever did before.

Dr. Dawn Hershman: Just to add to that. I think one of the areas, Eric spoke about nausea, it used to be debilitating, used to be the number one reason why people couldn’t get their treatment. And with a lot of research now there are so many drugs, it’s just not an issue anymore. So few people really suffer.

Now, it’s not totally gone, but it’s so much better than it used to be.

Dr. Eric Winer: You always have to be careful when an oncologist says that something’s well tolerated.

Dr. Dawn Hershman: Exactly. One of the reasons why-

Dr. Judy Garber: Except Dawn.

Dr. Dawn Hershman:  … a lot of women didn’t want to get chemotherapy is because they didn’t want to lose their hair. And in the past couple of years we’ve made enormous progress with some treatments to preserve women’s hair, and that’s a really big quality of life issue for people now that we’ve reduced the length of some of the duration of treatments, but women would still lose their hair and that was really devastating.

And to be able to offer somebody and say, “Look, it’s awful that you have to go through this, and I’m sorry you have to go through this, but there is one thing we can do to help you get through it, and maybe we can keep… maybe if you…” And what the treatment is called, scalp cooling, and Hope Rugo was one of the lead authors on that.

I know she’s a BCRF researcher and others. Some of the cooling technologies to preserve hair has been a huge improvement for people.

Dr. Larry Norton: Mary-Claire, I’m got to ask you this question because this is a question of historic importance. I’ll just read the question specifically. Are breast and ovarian cancer related? And if so, how?

Dr. Mary-Claire King: Thank you, Larry. I’m honored that you ask an option a medical question. They certainly are related. This reminds me to tell you one of my favorite mantras, which is that we, at least, we females are the most successful mammals there have ever been. We are fertile during a longer period of our lives than any mammal has ever been previously.

We are cognitively active post fertility longer than any mammal has ever been previously, and at the heart of both of these tremendous evolutionary success stories is estrogen. And estrogen is also at the heart of the relationship between breast cancer and ovarian cancer.

So while from the point of view of a geneticist and of course a lover of BRCA 1, it’s critical to think about the ways in which mutations in BRCA 1 and its sister genes predisposed to both breast and ovarian cancer and how we can prevent both breast and ovarian cancer by being aware of those mutations.

It is, I think from the point of view of a woman, enormously important that we think about the role of estrogens in all of this. And from that perspective, the activity of BCRF in supporting the work of my colleagues here who work on the basic biology of estrogens and how by understanding that basic biology, we can hope to modulate the effects in order to preserve for us are tremendous evolutionary advantages and our cognitive activity, and our looks well, well, well past, past youth.

At the same time to be able to modulate those effects so as to reduce the risks of breast and ovarian cancer both for women with mutations in BRCA 1 and the sister genes and for women who are mutation free. Thank you, Larry.

Dr. Larry Norton: Okay. Thank you. Judy, somebody here had their BRCA test 10 years ago and it was reported to them as negative for a deleterious mutation. Should they get retested?

Dr. Judy Garber: I think for many people the answer will be yes if they had enough risk of having a positive test to have thought about it before, and the test was negative. Now the technology would let you look more completely at the BRCA 1 and 2 genes and to look at other related genes.

But this is still a question you could ask your health care provider who should know, and if not, then in New York there’s no way to avoid genetics programs. They’re everywhere and you can ask a genetic counselor or a genetic health professional whether you should rethink testing.

It’s easy to do and still a blood test or a saliva test. It’s much less expensive than it used to be and it is more complete.

Dr. Larry Norton: I would mention the whole idea of genetic counseling really started with Joan Marks working closely with Mary-Claire. Very early days when we didn’t really know anywhere as much as we know now. She was a recipient of an award from BCRF many years ago really for that work, and I just want to call her out as somebody who really started a whole field that I think has been extraordinarily productive.

Can BRCA genes skip a generation? This is somebody whose mother actually had deleterious mutation and she got tested and was negative, but she’s still worried about her kids getting the abnormal gene. Go ahead Judy. Quick answer.

Dr. Judy Garber: So unless my colleagues have discovered something else recently, I don’t think so. Genes cannot skip a generation. They have to go from parent to child, but you do have to remember that we’re not the only parent. The other parent could have inherited a gene that may not have been tested for, that also could be transmitted to the child.

But in general, if you have tested negative, you cannot pass this onto your children. They don’t need to be retested to confirm that.

Dr. Larry Norton: Okay.

Dr. Eric Winer: I think what’s confusing is that diseases can skip a generation because just because someone doesn’t have breast cancer doesn’t mean that they, for example, didn’t inherit an abnormal BRCA gene or, this applies to other illnesses as well. But genes are pretty certain

Dr. Judy Garber: Certain. That’s not qualified unless somebody else is willing to stand up and say otherwise, they don’t skip a generation.

Dr. Larry Norton: I hate to say this, but it’s very important to say it. A surprisingly high percentage of people have a father that’s different than they think they do.

Dr. Eric Winer: I knew that was coming.

Dr. Larry Norton: All right.

Dr. Judy Garber: I did try to point out there was another parent.

Dr. Larry Norton: And the scary thing about that is when I ever make that statement, all the women in the audience laugh and the men stay stony silent with a heart. So I just want to emphasize that. And the whole question, I think this is going to evolve over the next two or three years even very, very quickly, the whole notion of family history being the best predictor of who should be tested and whatever.

And Mary’s written extensively about this and there’s a lot of discussion and we’re seeing a big movement toward more testing rather than less. But I think we’re going to leave that for subsequent discussions because it’s really such a big topic and we should have really formal presentations on this.

Dr. Larry Norton:  Dr. Chandarlapaty recently joined the scientific advisory board BCRF as has Eric indeed, and the question really is, people are hearing a lot about blood testing for diagnosis of cancer and for screening for cancer.

Dr. Larry Norton: I’ve seen ads on late night TV myself in this regard for following patients who’ve had cancer. It all relates basically to test for DNA in the blood. What do you think of that?

Dr. Sarat Chandarlapaty: This is an amazing research opportunity for us to be able to noninvasively look for biomarkers that can tell us about cancer that may still be there or that may be getting worse on therapy. It is still very much in the research realm. However, we don’t really have a current test that we can widely give to either detect cancer as a screening modality or else to modify treatment.

Not yet, but I think that that’s something that we’re all working on in the research setting that I think is extremely promising, showing very robust results.

Dr. Larry Norton: Okay. Thank you. Laura Esserman, UCSF has something to add to that right here.

Dr. Laura Esserman:  It’s just as important that we think about personalizing screening and prevention in the same way. And we’re running a large national study called The Wisdom Study to test annual screening against personalized screening. And I think these kinds of tests we have to be very thoughtful about.

We don’t want to do a lot of things to people who have extremely low risk because you’re likely to do more harm than good. So I think a personalized screening approach may be the perfect way to find the very populations at the highest risk where a different kind of testing are earlier detection may make a big difference and where you’re going to do less harm and a lot of good.

Dr. Larry Norton: Good. Laura, thank you. Lisa Carey, are you around? Why is everybody who I’m asking is sitting way in the back here. Come up to the forward because the people have heard that you can actually design studies that are targeting DNA abnormalities and mutation status rather than the diseases, and they’re calling them basket trials.

You gave a really superb talk about this yesterday to the scientists in our symposium. What’s your current feeling about the notion of treating the molecular abnormality rather than treating the disease specified by the organ, which it arose?

Dr. Lisa Carey: Well, I think the world of cancer therapy is absolutely moving towards using the molecular aberrations as the guide to what targeted therapy is going to work the best because that also allows you to emphasize the effectiveness and minimize the toxicity, so there is no question that we need to do that.

It does get complicated and I think in some of the ways that Larry is mentioning, we can’t underestimate the complexity of this. And there have been studies where people had super effective drugs for melanoma with particular molecular problems in their DNA and they just assumed the drug would work the same if you found that same molecular abnormality in a colon cancer and it doesn’t.

And the truth is that cancer, the biology is very, very sophisticated and complicated, and so it’s not easy. So you need our scientists who actually help inform what we’re studying and how we’re studying it. And we have to look at things in a system-wide way and not just assume that looking at one thing at a time is going to work.

Dr. Larry Norton: Excellent. Thank you. Obesity is bad for you, we all know that. But is it the obesity or is it the things you are eating to make you obese that is the bad thing? In other words, if you happen to be overweight or even on the obese side, but for some reason there’s some genetic predisposition to fat accumulation in your body and you’re actually, you’re eating a fairly healthy diet.

This one zeroes in specifically on dairy, but I think is a general question. Is it the fat in your body or is the things you eat to make you fat that’s important?

Dr. Neil Iyengar: I think that’s an excellent question and it gets back to this notion of understanding individual biology. I mentioned earlier that we find this fat tissue dysfunction in up to a third of people who are normal weight, who are not defined as obese. And in fact there is a small percentage, up to 10% of individuals who do meet the definition of obesity, who actually have functioning fat tissue and healthy fat tissue.

And so I think that there are components one can develop the bad biology of obesity independent of what body weight is through their lifestyle, but that’s not the whole story. There are certainly genetic predispositions, environmental factors that contribute to whether or not a person’s metabolic state is actually healthy or unhealthy and is going to contribute to the growth of cancer.

So the short answer to that question is it really depends on the individual, whether or not it’s their underlying metabolic state or it’s their lifestyle or a combination of both.

Dr. Larry Norton: Superb answer. This is a recurring question, which I’m just going to talk about here. Do you want to answer that briefly, Joyce? Mic over there, but then I want to make a general comment.

Dr. Joyce Slingerland: A lot of people ask the question, is there good fat and is there bad fat? Am I a fat person who has okay fat? And I think we don’t know a lot about how the microbiome and the specific components of our diets-

Dr. Larry Norton: Define microbiome.

Dr. Joyce Slingerland: Microbiome are all of the bacteria that are part of our normal body in our skin, in our gut, in all of the openings to our body, our nostrils, our vagina, and all of those other places. There are ways in which our body interacts with the environment that influence putting on weight, et cetera.

So there are a lot of things we don’t know about fat, but one of the things that I think is really an important take home message is that interventions that reduce weight have been shown to affect survival from breast and colon cancer, so bariatric surgery in individuals who are obese has been shown to influence survival from breast and colon cancer.

And interventions, there’s very active ongoing investigation to see whether lifestyle interventions with diet and exercise impact survival from breast cancer and the answers are not yet all in. But I think there’s very clear evidence from biomarkers that blood tests and markers of inflammation do go down with exercise, and estrogens do go down with diet and exercise.

And so if we can influence by weight loss, the biomarkers are bad outcome of breast cancer, it’s probable that we will influence things. And I think the take home message is wait, wait, wait and wait. There’s probably not good fat… There may be details of good fat and bad fat, but for the majority of people, getting rid of it is what really matters most.

Dr. Larry Norton: There’s a recurrent… Thank you. Just two comments, one quick editorial is that when we first started doing the symposium, we talked a lot about the cancer cell and you’d hear we’re talking a lot about other kinds of tissues in the body that are very related to the cancer, white blood cells, fat cells, even bacteria that exists in the GI tract.

The whole picture of what is cancer is rapidly evolving. The leaders in the field are all around the room or dispersed among you in terms of answering these questions, and I think that’s an extraordinary, exciting time biologically. The other point that I wanted to make is that… It’s a recurring question is, you folks are saying a lot of smart things.

How does my doctor know these things? How do I get this information? Am I getting too much therapy? I’m getting too little therapy. What about side effects? How can this be handled? I think one of the important things that BCRF is going to be… is already involved in it, Judy already mentioned something called The B4 study, which is a study of genetic predisposition.

But a very important component of that can often sitting in the front row, instrumental and others in the room in this regard is how to disseminate information, how to educate people about themselves so that they can then ask the right questions and get the right answers that are really specific for them.

We’re not very good at this yet, frankly, and I think that it’s not something we’ve emphasized in a whole lot in the evolution of healthcare, but now’s the time to do it and it’s something BCRF really needs to focus in on. Eric is dying to say something, and then Dawn who’s going to say something to you after that?

Dr. Eric Winer: Want to go first?

Dr. Dawn Hershman: I was just going to say, we now have many technological tools. Healthcare technology has advanced a lot to help us disseminate information better. Things like Twitter, you see like important results getting disseminated very quickly.

You see that there are social networks that help doctors that are from areas where they may not have experts to ask questions to experts to get answers quickly that we can make the world a lot smaller by using technology, and that can help us disseminate information all over the world.

Dr. Eric Winer: Great. Two quick comments. One, we are in the midst of conducting a very important national study that there may even be people in this room who are participating in, which is asking the question that if you’re a woman with breast cancer and you are presently overweight, does intervening with an intervention that seeks to reduce weight, whether that changes your chance of having a recurrence of the cancer.

They’re going to be 3,000 women enrolled in that study. There are already about 2,000 enrolled. It’s being conducted by one of our colleagues, Jennifer Ligibel and many others working with her nationally and it’s really important.

The other comment that I just wanted to make is, comes back to the importance of research. And it’s not just about drugs of course. Drugs, you can only take when the FDA finally approves them, and so when something’s being studied, it’s not necessarily easy to just take a drug.

That’s not always the case with other sorts of interventions, or circulating DNA, or a variety of different tests or interventions that don’t necessarily need to be FDA approved. But I think it’s very important that we’re rigorous about how we evaluate these things. And I’m sure Sarat would agree with me that in terms of circulating DNA that companies are advertising.

At the moment, we have to be very careful about how we apply those kinds of things in practice until we have more information. And so just because something’s available doesn’t mean you should rush to get it.

Dr. Larry Norton: My favorite quote is, Mark Twain, “It’s not what you don’t know that gets you in trouble, it’s what you know for sure that turns out to be wrong.” And in healthcare, this is extremely important.

I’m just underlining what Eric has just basically said is that the big change in this regard is, I guess, also part of the digital revolution is that on the basis of almost no information, or false information, or manipulated information, or very preliminary information, you can have big changes because of the dissemination of the recommendation via social media tools and basically change the landscape in ways that we can’t ask the questions really anymore and get to the definitive answers.

So it’s extremely important to have definitive answers before you proceed. And there’s lots of people, by the way, and New York city has become really one of the hotbeds for all sorts of alternative ways of treating cancer. People getting all sorts of infusions of things that are supposed to prevent cancer, and prevent heart disease, and other things.

You can go into any health food store and shelves, and shelves, and shelves of various products, each one of them is promising wonderful things. Be really careful. I’ve said this from this podium before, but I’m saying it again, is there is evidence and then there is superstition. Opinion is not valid, you really want evidence.

Science is really important, supporting science, following science, evaluating things scientifically is important for you as an individual as well as for all of us as a society. There’s another question that comes up, that’d be a third card is about immunotherapy for breast cancer.

And so Jedd Wolchok is sitting right here, one of the great… We have many leaders of the field basically in this room as well, but I’d like to ask Jedd to talk about current status from your point of view, is immunotherapy for breast cancer primetime?

Grab a mic over here.

Dr. Jedd Wolchok: It only works if I stand up? Okay.

Dr. Larry Norton: Yes.

Dr. Jedd Wolchok: I’ll try not to read into the fact that you introduced the immunology question with is the superstition or not. So I think-

Dr. Larry Norton: Those were two unrelated thoughts.

Dr. Jedd Wolchok: Okay. All right.

Dr. Larry Norton: That’s your own paranoia there, so go ahead.

Dr. Jedd Wolchok: I guess I’ve been working with you for too long. So I think that we’re very aware that immunotherapy has emerged as another standard way to treat some cancers, and melanoma and lung cancer, bladder cancer are some of the more well-known ones where they’ve made a very significant impact for some patients with those diseases.

More recently, I think it’s quite clear that a subset of patients with breast cancer do benefit in a modest way, and these are of course patients with triple-negative breast cancer where we think that the biology and the genomic landscape, the pattern of mutations that make the cancer perhaps look different than the normal breast tissue is more prominent in triple-negative cancer.

And that when combined with chemotherapy, an immunotherapy that blocks a pathway called the PD1 pathway, which is essentially a molecular break on the immune system can lead to more patients having regressions. I think it’s an important first step. It’s clearly not the end of our investigations in how to best use immunotherapy in breast cancer.

I think we need to understand more about why other breast cancers may not be as responsive and what we might do to try to remedy that. So I think now in 2019, immunotherapy is a standard approach to treat breast cancer, specifically triple-negative breast cancer, but we have much more research to do, the importance of which was emphasized by Larry. Thank you.

Dr. Larry Norton: Thank you. I passed out a couple of cards because there were a couple of questions I think are specific to presenters. Eric, brain metastases.

Dr. Eric Winer: Is there a specific question or…?

Dr. Larry Norton: Where do we stand in the treatment of brain metastases?

Dr. Eric Winer: In certain types of breast cancer, so for example, HER2-positive and triple-negative breast cancer, brain metastases or the cancer spreading to the brain is actually relatively common during the course of someone who has advanced breast cancer. Very uncommon to be the first place that that cancer shows up again after a woman has been treated for breast cancer.

But again, in somebody who is living with advanced breast cancer, it’s relatively common, and it can happen for that matter in women who have estrogen-receptor-positive breast cancer as well. Our treatments have gotten better. There’s still a long way to go and we have challenges, and I talked a little about this yesterday at our retreat, but some of those challenges are that the brain probably doesn’t allow drugs to get in as readily, although it does allow some drugs to get in.

There may be differences in the tumor microenvironment in the brain or in the microenvironment such that brain tissue is different for fairly obvious reasons than many other parts of your body. And there may be some specific genetic changes that occur in these tumors or tumors with specific abnormalities may tend to spread to the brain, and we need to understand all of that better.

There are many people working on new drugs for treatment of brain metastases and the FDA has recognized the importance of this. And finally, I think that we can’t underestimate the importance that has been played by surgery and some new and much, much more specialized radiation techniques and treatment.

So by no means is this a happy story in breast cancer. We don’t want to see patients whose cancer spreads to their brain, but people can live with that complication and live with it well at times for much longer than was ever the case in the past. And I think we will continue to make progress, but we need support.

Dr. Larry Norton: Thank you, Dawn.

Dr. Dawn Hershman: I guess two things. One, I just wanted to comment on the issue of supplements because we’ve done studies that have shown that certain supplements, people were taking to prevent the neuropathy that Dr. Winer was talking about, actually can make it worse. And the critical importance of doing the rigorous studies is not just tell people what to do, it’s also to tell people what not to do.

So it’s not just about us having a perception that these things can be harmful, there’s evidence that these things can be harmful, so it’s important to do the research. The question on the card was, “Should I be taking hormonal therapy for 10 years? What’s the optimal duration of hormonal therapy to take?”

I think it’s very confusing for people because it’s hard enough to get through the first five years, let alone to get through 10 years or even longer. And that’s again where the whole concept of personalized treatment comes up. A lot of the benefit for longer duration hormonal therapy is actually to prevent a new breast cancer.

So are you at risk for developing breast cancer? Do you still have your breasts? Those are important questions. I think we’re moving into, do you tolerate the hormone therapy? What is your risk to begin with in terms of the cancer coming back? And I think what’s really exciting is that there are a lot of molecular tests being developed that may help guide these decisions to help figure out who’s actually at risk for a late recurrence so that we can guide those answers better in terms of who should be on treatment longer versus not.

Dr. Larry Norton: And that work is connecting to cell-free DNA and monitoring, and I think it’s a really rapidly evolving, very exciting field. Neil, I can’t resist this one because this one is about yoga. Neil Iyengar… No, it’s true, he’s from that family.

Dr. Neil Iyengar: So we have a few poses?

Dr. Larry Norton: He’s the only person I know you can have a conversation with him while he’s standing there and putting his foot behind his neck. Health benefits of yoga and potential dangers of hot yoga. What are your thoughts?

Dr. Neil Iyengar: Okay. Well, I’ll start a little more generally. There has been work, important work looking at yoga and we know that from the standpoint of mental health interventions that emphasize mindfulness, as well as more structured interventions like cognitive behavioral therapy and so forth, can be effective tools for managing a lot of the side effects including anxiety or mood changes that accompany breast cancer treatment.

And certainly yoga is within that toolbelt of potential interventions that can be incredibly helpful for managing those types of side effects or not even side effects, but just general experiences of individuals who are either at high risk or have developed breast cancer.

We are learning about the specific effects of certain types of exercises or physical activity behaviors, and there has been some preliminary work looking at yoga and other types of lower intensity exercise on metabolic factors, and I think that that’s an exciting area of research as well.

So for now, all I can say is that we know from the mental health standpoint that yoga is incredibly helpful for some people. And to answer the hot yoga question, I’m afraid I don’t have a good answer to that right now other than it is important that we think about safety for any type of intervention, be it a drug or be it physical activity.

And that’s why one of the things that we are doing is taking a drug development approach to the development of exercise in, for example, phase one trials to find the right dose of exercise, the right type and dose of exercise, phase two trials to determine if that dose is effective in helping to shrink tumors, and ultimately phase three trials to look at survival.

And this is the kind of research that we need to do to develop lifestyle interventions.

Dr. Eric Winer: I’m trying to decide if I want the treadmill shipped to my house or the personalized yoga instruction.

Dr. Judy Garber: Both.

Dr. Neil Iyengar: I would say both attractive opportunities.

Dr. Larry Norton: Eric, I think we going to have to randomize that one. I think that’s clearly a randomized question.

Dr. Neil Iyengar: That will be my next [crosstalk]-

Dr. Larry Norton: We have only a couple of minutes left, so I’m going to get myself into real serious trouble here because one of the questions is, on several of the cards, why is there so little research on metastatic breast cancer? But the fact is that BCRF has had a huge imprint, and I’m going to ask Dorraya, actually, I’m shocking you.

I know you’re going to beat me up for this afterward. Come on right here, I’m going to give you the mic. She’s really our new Chief Scientific Officer. Recent recruit has done a spectacular job. I just want to emphasize, everybody thinks that the BCRF is like us, there it is.

BCRF in terms of the science has an extraordinary small, but extraordinary effective scientific leadership group that Dorraya is now running, Maneesh who’s not… He just doesn’t hand out mics, but he’s also been incredibly involved. And Margaret Flowers is here somewhere, Sarah Boll.

Why are we doing so little research on metastatic breast cancer?

Dr. Dorraya El-Ashry: Hi. We don’t do so little research on metastatic breast cancer at BCRF. Since 2011 alone, we have invested over $160 million in metastatic breast cancer research. And at BCRF, metastatic breast cancer research goes along two pathways. We have the Evelyn H. Lauder Founder’s Fund, which is focused solely on metastatic breast cancer and incorporates both basic research, but also clinical trials, and that has a $31 million to date investments in it.

And then in our annual work program of which many of the investigators are in this room, this year alone, we have $27 million, which is more than 40 percent of the BCRF investment total for this year in metastatic breast cancer research. So if we go back over the years, at least a third of all the investment in BCRF, in research is in metastatic breast cancer research.

It is the area that was my own research area. It is near and dear to my heart and I will steward BCRF to continue to keep this as a high priority of investment in metastatic breast cancer research.

Dr. Larry Norton: Thank you. All right. We’ve run out of time, we’ve got a ton of important questions here, some of them are rather specific. I’m trying to figure out some way that I can get the answers, people to answer that question and maybe BCRF’s blog or some other means that we can… Some of these have more general topics so we’re going to get to it.

I thank all of you for being here, for answering these questions. My extraordinary panelists, all the scientists who are around you, thank you for being here. Let’s have a great lunch.

Outro: That was BCRF’s 2019 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.

Subscribe to Investigating Breast Cancer here:

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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.