Breast Cancer Research Foundation https://www.bcrf.org/ The mission of the Breast Cancer Research Foundation is to prevent and cure breast cancer by advancing the world's most promising breast cancer research. Mon, 08 Apr 2024 15:58:26 +0000 en-US hourly 1 https://www.bcrf.org/wp-content/uploads/2023/01/favicon.ico Breast Cancer Research Foundation https://www.bcrf.org/ 32 32 Broadway Stars Align to Support Metastatic Breast Cancer Research https://www.bcrf.org/janice-jam-breast-cancer-research-2024/ Mon, 08 Apr 2024 15:30:52 +0000 https://www.bcrf.org/?p=26835 Money raised from the second annual The Janice Jam: Broadway for Breast Cancer will fund BCRF research to end metastatic breast cancer

Some of Broadway’s biggest stars will shine even brighter when they come together for “The Janice Jam: Broadway for Breast Cancer,” a benefit concert supporting BCRF on May 13. One hundred percent of the net proceeds will fund the groundbreaking research of BCRF investigators—specifically, studies focused on metastatic breast cancer (MBC), an incurable form of breast cancer.

The Janice Jam was created by Broadway performer Matt DeAngelis, who has appeared in Waitress and Hair, among many other productions. After the tragic loss of his mother, Janice, to MBC in 2022, Matt wanted to find a way to pay tribute not just to her but to everyone who has had or is currently living with the disease. Janice adored the theater, so putting on a concert with his fellow Broadway stars felt like the perfect way to honor her while also raising awareness and funding for breast cancer research.

“She was kind of a Broadway mom,” Matt said of Janice during an appearance on the TODAY show last year. “She was so, so thrilled that I was an actor, and she was friends with a lot of my Broadway friends.”

Working with his wife, fellow performer Christine Dwyer, he founded The Janice Jam, a charity event that brings together Broadway industry friends and colleagues for a night of unforgettable vocal and dance performances.

This year’s show will be held at Haswell Green’s in New York City on Monday, May 13. Featured performers include Jackie Cox, Caissie Levy, John Gallager Jr., and more. As he did at last year’s concert, Matt will also perform.

BCRF was selected as the event’s beneficiary because of its dedication to metastatic research. This year, the Foundation is the world’s largest private funder of metastatic breast cancer research—investing more than $22.3 million into the form—and the highest-rated breast cancer research organization in the country.

“This event serves as the celebration of a woman who was more than just an honorary part of the Broadway community, and I am so proud of how we continue to build this as a means to education and celebration,” Matt said. “With continued education and non-profit support for future generations, we are proud to do our part in helping eradicate this disease, thus, preventing losses like mine and many others in this world.”

BCRF is honored and grateful to be the recipient of proceeds from this year’s concert. Funds will support researchers seeking to advance our understanding of metastatic disease, find new therapies to help those living with it now, and more.

“By supporting BCRF, The Janice Jam is driving change to improve outcomes and save lives,” said BCRF Chief Scientific Officer Dr. Dorraya El-Ashry. “In 2024, an estimated 200,000 people are living with MBC, up from 140,000 in 2014—evidence that we are successfully extending the lives of metastatic breast cancer patients thanks to improved treatments. More women are living longer, and we are accelerating progress so that all women can live without the life-threatening power of MBC.”

The Janice Jam couldn’t happen without a group of talented, committed volunteers handling everything from event production to publicity, including Tami Eagle Bowling, who is currently living with metastatic breast cancer.

“I will never forget the day I heard the words that my breast cancer diagnosis was incurable because it had spread to my liver,” she said. “I am grateful for people like Matt and the incredible Broadway community who recognize that research is the only way to end death from breast cancer and give patients more time with their loved ones. The positive energy that fills the room at this event gives me hope.”

Purchase tickets for The Janice Jam or make a donation here.

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Improving Treatments for Invasive Lobular Carcinoma with Dr. Adrian Lee https://www.bcrf.org/2024-podcast-dr-adrian-lee-invasive-lobular-breast-cancer/ Thu, 28 Mar 2024 16:30:33 +0000 https://www.bcrf.org/?p=26740 Dr. Lee discusses collaboration, strategies to improve treatment for ILC, and more in this latest episode of investigating breast cancer

Over the last few decades, scientists have discovered that breast cancer is not one disease but many. Understanding the differences between various types of breast cancer can lead to innovation, more effective treatments, and more comprehensive approaches in research overall. One breast cancer that researchers are uncovering new treatments for is invasive lobular carcinoma (ILC), also known as invasive lobular breast cancer. It’s the second most common form of breast cancer in the U.S. and accounts for 10-15 percent of diagnosed breast cancers, but it has long been misunderstood and understudied. As Dr. Adrian Lee’s research demonstrates, the unique biology of ILC requires new treatment and new ways of thinking.

The goal of Dr. Lee’s laboratory is to translate basic cell and molecular research findings to breast cancer treatment. With fellow BCRF investigators Drs. Steffi Oesterreich (Lee’s wife) and Jorge Reis-Filho, he launched a first-of-its-kind ILC biorepository, which was made possible by a legacy gift to BCRF from ILC patient advocate Leigh Pate. A BCRF investigator since 2013, he is the Pittsburgh Foundation chair and director of the Institute for Precision Medicine at the University of Pittsburgh and UPMC. He is a professor of pharmacology and chemical biology and a professor of human genetics at UPMC Hillman Cancer Center and Magee Women’s Research Institute.


Read the transcript below: 

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

Dr. Adrian Lee: Thank you for having me.

Chris Riback: I thought we should start with the context and two topics that jumped out to me in regards to you, and I’m certain they’re connected and you’ll help me understand exactly how. One, of course, is precision medicine, which you seem to have dedicated your career to. And the other is invasive lobular cancer, which we may end up calling ILC. So let’s start with the former. What is precision medicine and why did it speak to you?

Dr. Adrian Lee: Yes, so I think we’ve been very fortunate in breast cancer to be leading the charge in precision medicine. The idea of precision medicine, it’s a relatively new concept. It was only coined in 2011 so we’re 10 years into this. But it is the idea that with these great new technologies and our ability to understand the molecular features of disease, rather than calling a disease by the symptoms or the person who found it, that’s traditionally the way, why don’t we call it by the driver, the mutation, or the DNA change or the protein change, that’s causing the disease? So breast cancer has led the charge in that. For example, estrogen receptor–positive breast cancer was because estrogen receptor was identified 40 years ago. So in breast cancer, we’ve had this way to be more precise about describing the disease and a better description allows us to be better about treatment of the disease. And so I’ve been keen to use laboratory research to try and better define the disease.

Chris Riback: And it’s so interesting to hear you frame it that way because as I was researching and thinking about it, I kept coming across almost-interchangeably precision medicine and personalized medicine or personalized care. And that description, it makes sense why the growth, if you can kind of chart it in personalized care and I would imagine as well the transformation in the thinking around prevention care once somebody has cancer, even the progression of the growth of the personalized aspect of that care must be directly aligned with the development and growth of precision medicine. Am I understanding correctly?

Dr. Adrian Lee: Yes. And maybe I could just say one sentence on that because I teach this and it’s quite a confusing area. So healthcare has always been personalized. The way the physician asks you about your personal history relates to your risk and treatment in the future. So that was always personalized. The difference is now it’s precise based upon our ability to measure these features, be those features in the tumor or be those features in blood. It’s precision medicine leading to personalized healthcare, enhancing our personalization of healthcare. And in breast cancer, we have this array now of tests that allows us to really define the disease and try and give the right therapy to the right person at the right time. Tailoring better efficacy and lower toxicity, for example.

Chris Riback: That’s super helpful. I appreciate your increased precision in the explanation. And I promise I would be the student coming to you afterwards and saying, “Well, professor, can’t I get partial credit on this answer? I mean, I didn’t get it completely right, but at least half credit here, please.”

Dr. Adrian Lee: I ask that question. I ask when I teach it, I ask that on my grading exams afterwards. I ask that exact question and see what their answers are and it’s quite interesting. I think over time, people have become more comfortable with the term “precision medicine.” You might remember that President Obama, I think it was 2015, had the Precision Medicine Initiative.

Chris Riback: Oh, no. I don’t.

Dr. Adrian Lee: So in that, the government gave $100 million to start the kind of catapult of what’s happening with precision medicine. And they started something called the Precision Medicine Initiative, which is now called All of Us. And in All of Us, a million individuals are donating blood and biometrics. They already have done this on 750,000 individuals and that led to the great rise in the use of precision medicine and, I think, in the understanding of it as well.

Chris Riback: There may be a book there, professor. So let’s move to invasion lobular cancer and what is unique, if you would help explain for me, in its biology that distinguishes ILC from other ER-positive diseases.

Dr. Adrian Lee: Yes, so that’s a great kind of follow on from precision medicine is that what precision medicine says is that if we can better define the disease, the taxonomy of the disease, what makes the disease, we can then better understand it and better treat it and get better outcomes. That’s the premise. And ILC is like that.

So invasive lobular cancer, or ILC, is a histologic subtype of breast cancer. It accounts for about 10-15 percent and it has a very specific change which the others don’t have. It has a mutation in a gene called E-cadherin, its gene name is CDH1, and this is a protein that causes cells to stick together. And when you mutate that gene and you lose that protein, cells now can’t stick together. Because of that, it has very unique features, which is very different from the other [breast cancers], and those features are important clinically. So because the cells don’t stick together, they grow very differently and they’re very difficult to image the tumors.

So a fundamental understanding of the molecular basis of the disease, the E-cadherin mutation, leads to the phenotype, the different growth, which leads to a problem with imaging. So that’s the premise of precision medicine that we should probably pay attention to that. That leads to other features. Because it’s difficult to image, it tends to be detected later, which is bad. It has different types of recurrence, it tends to recur later. And then it has different sites of metastasis, very different sites of metastasis. So all of that is related to the original definition of disease, the precision medicine, if we can measure the mutation.

Now, funnily enough, we’ve known this for years. For 40 or 50 years, pathologists have looked and said, “Oh, this is a different type, 10 to 15 percent. So 40,000 cases a year of this unique type.” But there was really no research to try and understand why or what’s the importance of that. It was simply lumped together with the more common form. So I run the laboratory with my wife, Steffi, and she was really one of the pioneers in forcing this field forward and in the last 10 years have made fundamental understandings and increased awareness. You would say 20 years ago, if you look in the records, people just won’t consider it. Now I think it’s kind of come to the forefront that people should be trying to understand this.

Chris Riback: And as I understand it, you are focusing on inhibiting tumor growth. And what I found myself wondering was does that mean tumor growth from zero to the first stage, which as a lay person I would characterize as prevention or early spotting? And I’m hearkening now to what you just said a moment ago that one of the characteristics of the cells not sticking together is that they become very difficult to image, and so one sees them later. So I’m wondering is that what you are kind of focused on? Or we’ve identified the tumor finally, or I’m sure part of what you’re working on is trying to identify it obviously as early as possible, but we’ve identified it finally and now we want to prevent it from growing further. So we’re in the spectrum, or is the answer to that, “Yes, everywhere in the spectrum”?

Dr. Adrian Lee: That’s a great question. I haven’t been asked that before, but I think it’s very thoughtful, the question. It’s very hard to study the early parts of the disease. To do prevention research, it’s incredibly difficult. We don’t have many good models of it. And in humans, the disease when we detect it is already there so it’s just hard to do that. Our current goal is really a focus on, as you said, the established disease and how do we treat it? So nearly everyone dies of metastatic breast cancer. They don’t die of that early disease. If we can catch it early enough and do surgery, we can cure most of those patients with surgery, radiation therapy, and standard therapy. But it’s the patients, 40,000 dying a year from advanced or metastatic breast cancer. We really, in our lab, are focused on that.

I think it is true that most approaches to treatment in that setting might relate to preventional treatment of the early disease. So, if you take, for example, hormone therapy, tamoxifen [this is true for HER2 therapy as well] most of them act very well in the advanced setting, they work well as adjuvant once the disease has been cut out, and then they also work as tamoxifen for prevention, for example. So I do think that many of these ideas we learned from helping reduce the rate of death from metastatic breast cancer might be moved into earlier settings, but we don’t study that in our lab per se.

Chris Riback: And so let’s talk about the part that you do study and inhibiting the tumor growth. Talk to me about your studies there please.

Dr. Adrian Lee: Yes. So to try and put this in simple lay terms, when you lose this E-cadherin gene, something has to compensate for that because the cells have to adapt, because now they’re not stuck to each other. They’ve lost their natural environment and so they’ve adapted. And if we can identify those adaptions, those are probably requirements for them to grow, that maybe that’s a dependency that we can then block and then kill them off. The E-cadherin isn’t there so we can’t target that, but we can target the thing they’re now dependent upon, or this requirement. So we have ways in the laboratory where we can identify those dependencies and then target them. And the most exciting thing is what we study in the BCRF grant is that one of the things that happens is that when the cells don’t bind to each other with this E-cadherin, now it’s not sticking the cells together.

What happens is this frees up growth factor receptors that drive growth and they become hyperactive. And this has been shown by us, been shown by a number of groups now, and that gives you a potential therapeutic target because we target these pathways all the time in breast cancer. So we first showed that the loss of E-cadherin upregulates a classic growth factor pathway called IGF1 receptor, and there are drugs targeting that in clinical trials. And most recently, we showed that it also upregulates HER2, which is one of the major drivers of breast cancer and there are lots of drugs available for that. So this is this kind of translational relevance. We’re trying to identify these therapeutic vulnerabilities. Hopefully, we have drugs already available or FDA approved, and we can then use those in our models and hopefully move those into clinical trials.

Chris Riback: And so the part that folks always become interested in, which is rubber actually hitting the road, where are you in the stages of those studies? Are you re-finding patients or people to join? And what’s your hypothesis?

Dr. Adrian Lee: Yes, so I think the pre-clinical laboratory and pre-clinical data is very solid. I mean, you have different levels of confidence. I’d say probably it’s the highest level that this, we’ve done as much as we can relatively do. And so now, as you said, the rubber has to hit the road. Does it work in the clinic? And sometimes it does and sometimes it doesn’t. Maybe our models are wrong, for example. So we have been discussing the idea of testing these growth factor receptor inhibitors, specifically in lobular cancer. And I think there’s a number of clinical trials in development that are floating around to do that. I think there’s quite a lot of interest from pharmaceutical companies to do that.

So, there’s a number of concepts at the moment where we will do trials, specifically in lobular cancer, to try and understand better imaging, for example. Such that we can better understand response and then tailor the therapy, make sure that maybe we will increase, put in this growth factor receptor inhibitor, or maybe we’ll decrease some form of chemotherapy. So we have quite a few of those trials now in development.

Chris Riback: Excellent. And when you do work like that, does it involve, so there are so many clinical trials going on obviously. There are so many, let’s call them, banks where various samples are being collected. Do you do this type of work by connecting with those types of groups or other partners, or do you need to create a unique cohort and that one very hard part of the job is getting that cohort together? How do you attack the problem?

Dr. Adrian Lee: Yes, so I think that’s generally been the problem with lobular cancer. Because it’s only 10-15 percent of the whole of breast cancer, any one study doesn’t have enough to have the power because the study is powered on the total. And then if you take 10 percent of it, it’s never going to have the statistical power of the whole thing. And so you need the community to come together. And actually, that’s what happened in the last five to 10 years. It’s like studying a rare disease, yes? It’s not rare, 40,000 women a year, but it’s rare compared to the total. So basically what we’ve seen is this real coming together of those groups to say, “Hey, there should be a focus on lobular.” We’ve now had lobular cancer as educational sessions at the San Antonio Breast Cancer Symposium. BCRF was very helpful in that they were one of the main sponsors of our recent ILC Symposium. So we held a meeting here in Pittsburgh in September 2023. That was the biggest yearly meeting. We had over 220 people come.

Chris Riback: Wow.

Dr. Adrian Lee: The audience of that meeting was a third physicians, a third scientists, and a third lay patients and advocates. That’s pretty unique. Normally, that would never be that. And that was a great opportunity to share these ideas and concepts, like you said, to share knowledge, share models, talk about tissue banks, all of those things. All those things you said came together. And particularly for something that’s challenging, like a rare subtype of this, you need to have community to get those things done. No one is going to be able to do it alone.

Chris Riback: That’s super interesting. So the fact that this was at Pittsburgh, obviously I’m assuming that means that you generated and ran or led the conference. I mean, that would seem extremely rare for researchers, scientists, heads of major departments and medical efforts, such as what you represent, to include patients, or advocates as you say, at a symposium on the topic. And please, you’ll correct me if I’m wrong, I would think that frequently the incentive is for scientists to talk to scientists or maybe scientists to talk with pharmaceutical companies or potential funders. One, am I right? And two, regardless of whether I’m right or not, what’s the inspiration and the thesis behind including people who maybe, let’s say, have the most stake in the game?

Dr. Adrian Lee: Yes, so I think that last statement is you summed it up, is the patient has the most stake in the game. I think they had somewhat been excluded for a number of years. Stephanie and I were lucky to be trained at Baylor College of Medicine, where they were one of the earliest to incorporate [patient] advocates into their specialized program of research excellence in breast cancer. So we had a training in needing to do it. And when we came to Pittsburgh, we formed an advocacy group immediately called the Breast Cancer Research Advocacy Network. This is a Pittsburgh local group that meets every month, about 15 women meet every month to discuss research and help researchers. And then when we held the very first ILC symposium that was held in Pittsburgh in 2016, I think 35 advocates came to that because it’s kind of natural to us that advocates should have a say and be involved.

And there was a patient there, Leigh Pate, who drove a lot of what’s happened in lobular advocacy. She was a tour de force. She had an incredible ability to communicate. She was an incredible writer. She unfortunately passed away recently, and she does have a legacy. She donated money to BCRF to develop this legacy, which is a biobank we’re developing of models of ILC that we characterize and then we’ll make publicly available to everyone. So I think it’s kind of all come full circle. I think her spearheading advocacy in 2016 really drove a lot of these groups to form, and now you have this huge international advocacy. I mean, she really was the pioneer for this. And there were many others involved, but she really kind of drove the subject.

And I think patients, particularly when it’s been understudied, have really raised awareness through social media, through advocating, and I think that’s been good. And it’s driven a lot of scientists to think, “Yes, I should be studying lobular.” It’s easy to do that easy science. Science is never easy, but you kind of drift to the thing that’s a bit easier. And it’s hard to study a disease where you’ve got to collaborate. That’s not easy so I think that’s been a good thing.

Chris Riback: What a remarkable legacy. Isn’t that a wonderful thing? Tell me about you. How did you get into this? Was it always science for you growing up or did you just marry into the business?

Dr. Adrian Lee: I married my wife into the business, yes. No, I got my Ph.D. in London and came to San Antonio. San Antonio, at that point, was the mecca for breast cancer in the US. That’s where the San Antonio Breast Cancer Symposium formed. Nearly all the top leaders were in San Antonio. And Steffi, my wife, got her PhD in Berlin and was recruited around the same time when we met and married, had our kids there. Breast cancer has always been a passion. I think both of us feel we are lucky to have a job where we’re doing our passion. It’s one of those kind of rare instances where our job is part of our life. Obviously, we have a work-life integration, not a work-life balance like many scientists, and our kids would tell you the same. They didn’t become scientists.

But I think we get great joy particularly, like you just said, with the advocates of seeing patients and explaining. We do a lot of lay presentations. I run the Correlative Science Working Group for the [BCRF-supported] Translational Breast Cancer Research Consortium, and I gave a lay talk about biomarkers to advocates last week. I think you said this, you were the one that stated this, they have probably the biggest stake in the game and we should be listening to them around toxicities, all of these things. They’re the ones facing that. And so I think we take their comments seriously, and we appreciate hearing from them.

Chris Riback: And growing up, was it always science for you? Was there a chance that you might become a great musician or that literature was a passion? Or from day one, you were busy experimenting with chemicals or something in your parents’ kitchen?

Dr. Adrian Lee: That’s interesting you say that. There’s no science in my family. I have four brothers. They all do something incredibly different. None of them do the same thing. One’s an engineer. One’s in big banking. One’s in computer science. My dad was a painter and my mom worked, but there was zero science. I think like many, I got the opportunity to work in a lab when I was 16, and it was very transformative. I have this passion to learn. I do. Like most scientists, I am continually wanting to learn. I’m not very satisfied to stop at the status quo. Every day is a different day in the lab. There’s never a day that we are just doing the same thing. Every day is, most days, “This didn’t work and we have to figure out what to do next.”

Chris Riback: Now what?

Dr. Adrian Lee: When it does work and you get a grant and you get a great clinical trial or a great translational result, it can be super fulfilling. And as an example of how it’s changing, one of the biggest things that’s changing is computational biology.

Chris Riback: Yes.

Dr. Adrian Lee: In your life, you’ve already used AI 15 times this morning, yes? It’s integrated into everything you do. Some people don’t want to believe that, but it is. It’s driving everything you do now, from your use of the internet to everything. And that’s true in our research as well. We’ve really had to adapt to learn computational biology. That’s one of my newest things is I’m doing a lot of high-performance computing, supercomputing. I wasn’t trained in any of this.

Chris Riback: Yes, wow.

Dr. Adrian Lee: I’ve learned it on the fly and it’s not an easy data sharing and handling and wrangling. Data is not trivial, but it is exciting to have another kind of stage and another kind of thing to learn.

Chris Riback: Yes, what a terrific opportunity. And I couldn’t agree more. The field for someone who is, let’s say, genetically inclined to be a continual learner, where that is instinctively a passion, you’re obliged to do that. In fact, people like you are partially perhaps to blame for it because you keep discovering something new and that necessarily requires continual learning and learning something new. I can understand why that’s inspiring, and I thank you and your wife and others like you for that continual work, that inspiration for the rest of us. And thank you for taking the time with me today.

Dr. Adrian Lee: Thanks for having me. Those were great questions. It was a very nice conversation.

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The History of Women’s Health with Dr. Elizabeth Comen https://www.bcrf.org/the-history-of-womens-health-with-dr-elizabeth-comen1/ Tue, 26 Mar 2024 17:47:08 +0000 https://www.bcrf.org/?p=26707 How breast cancer patients today grapple with long-embedded biases across all aspects of health and how we’re turning the tide

Earlier this month, BCRF investigator Dr. Elizabeth Comen joined BCRF staffer and breast cancer thriver Sadia Zapp for an Instagram live about the history of women’s health and how breast cancer patients experience care today. A student of medical history, medical oncologist at Memorial Sloan Kettering Cancer Center, and BCRF-funded investigator since 2011, Dr. Comen provides a unique point of view on women’s health then and now.  

Breast cancer, Dr. Comen noted, stands out in many ways in the history of women’s medicine. “We have dramatically changed the landscape of survival for breast cancer patients,” she said. “It’s an area that has gotten a lot of funding—but that doesn’t mean it doesn’t need more. It always needs more.”

Watch the interview below or read an edited excerpt of their conversation.

Breast cancer is a full-body experience. Treatment affects us from our head to our toes. Let’s start with the heart, especially since patients like me who have had chemo and radiation are at a higher risk for heart disease. What has informed the care of heart disease and how have things improved?

In general, women’s heart disease has been neglected in the history of medicine. One of the founding fathers of cardiology and of our residency system was a man named Sir William Osler. He did amazing things, but he also didn’t believe that women died from heart disease. And today, it’s the number one killer of women. I really wanted to unpack where this came from. There was one famous treatise that he had on cardiovascular disease, and he talks about the white-haired executive clutching his chest—being so overworked that he collapses and has a heart attack. But when it came to women, he said they had neurotic angina, hysterical angina, and he wrote that these women don’t die. And that’s it. Hundreds of years later, too many women are dying of heart disease worldwide.

There’s a lot of work being done right now to understand how chemotherapy, radiation, and hormone treatment may affect the heart. This is certainly an area that researchers are working on to try to uncover gaps and fill them in with research and data and clinical attention.

Can you talk to us about the genesis of plastic surgery and breast implants. What surprised you?

It’s really, really interesting for me, because here I am. I examine women all the time. We talk about implants. We talk about reconstruction. We talk about body image. And I had no idea about who developed breast implants and why. They were not developed because surgeons were trying to help women with their body image after breast cancer. I’ll leave it in the book, but a lot of it came from concepts of male gaze, what they thought would look good for women, and pathologizing.

The flip side is that there were some incredible people and advances, especially against radical mastectomy. We know that Dr. Bernard Fisher did [seminal] work to show that you could do [less-invasive] lumpectomy and radiation, and it was as effective as mastectomy. But throughout history, there were some doctors in the breast cancer space that just felt that breasts were useless appendages, and it would not be scarring for women to lose them.

That really struck a chord with me because obviously for breast cancer patients, body image is so integral to our experience.

There is this idea that women’s beauty is of value culturally. I think that vanity has its role and can be important for some women. The purpose of writing that chapter was to show the nuance there. For cancer patients, it is very important for some of them to address their needs in terms of how they feel about themselves. For others, maybe less so. What we really need to do is make sure that we’re talking to women about who they are and what actually matters to them. Do they want an aesthetic flat closure? Do they do they want implants? Do they want like to look a certain way? We need to meet the needs of the patient in front of us and not impose what we think is best for them based on our perceptions.

There’s a lot of talk about weight loss and BMI right now. Can you talk a little bit about BMI and what it means for patients.

The BMI is not how we should be measuring women’s fitness or their overall health. It is a gateway to determining if someone is morbidly obese. We know that we have an obesity epidemic in this country. But when we’re talking drilling down to look at a healthy woman, [it shouldn’t be done] through BMI. We need to have much better studies on women’s metabolic health and their muscle-to-fat ratio. We know from BCRF researcher Dr. Neil Iyengar that you can be what’s called “skinny fat” where you have a normal if not low BMI, but you have more fat than muscle. You can’t lift your groceries but you’re fitting in your size 2 jeans. Or maybe you’re on Ozempic but you’re not lifting weights, so you’re losing muscles and your bones are weak. We really, really, really need to move to a model of women’s health that it’s not just about being small—as we often message to women—but about being strong.

How has breast cancer research stood out in the history of women’s health?

Yes, not everything is bad about the history of women’s medicine. Breast cancer is a shining example, particularly in terms of research. It’s an area that has gotten a lot of funding—but that doesn’t mean it doesn’t need more. It always needs more.

But we have dramatically changed the landscape of survival for breast cancer patients, thanks in part to BCRF, which was founded by Evelyn Lauder and my mentor, Dr. Larry Norton. There are incredible examples, but I think as with anything, we can always do better. We need to address not just how women survive, but how they thrive, which is something BCRF is doing. I’m thrilled to be a BCRF grantee.

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Breast Cancer Treatments: Everything to Know https://www.bcrf.org/breast-cancer-treatments-everything-to-know/ Thu, 14 Mar 2024 15:02:15 +0000 https://www.bcrf.org/?p=26637 BCRF explores the evolution of breast cancer treatments, from surgery to cutting-edge targeted therapies, and the journey toward precision medicine

The breast cancer treatments we have today are the result of innovative ideas, painstaking research, and serendipitous discoveries that stretch over centuries. The evolution of breast cancer treatments started in 3,000-2,500 B.C. with the first historical mention of the disease’s existence in the records of ancient Egyptians. So began the journey to understand the underpinnings of breast cancer in order to develop and improve breast cancer treatments.

Today, breast cancer is the most commonly diagnosed cancer and the leading cause of death in women globally. But our approach to breast cancer treatment is steadily being refined as researchers leverage cutting-edge technologies to develop better and better strategies. And currently, many breast cancer treatment options are available.

Here, we discuss breast cancer treatments ranging from surgery—the first treatment for the disease—to newer systemic therapies for breast cancer and targeted therapies for breast cancer.

Breast cancer surgery

The defined structure of the breast made surgery the first and most obvious breast cancer treatment option. As exploration of human anatomy increased during the Renaissance Age, surgical techniques were refined and ranged from excision of an identified lump (now called lumpectomy) to removal of the whole area, including the pectoral muscles that lie beneath the breast (now called radical mastectomy).

Until the 19th century, surgical techniques remained relatively stagnant. Success was limited by the lack of disinfection and sterilization procedures, which meant women were more likely to develop an infection, and the risk of death was high. The lack of anesthesia also hindered good outcomes because surgeons had a short window of time to complete the process as they considered a patient’s tolerance for pain.

Advances in breast cancer surgery promoted better outcomes from breast cancer as did other breakthroughs such as:

  • Blood transfusions
  • Invention of the microscope, which allowed normal cells to be discerned from cancer cells
  • Discovery of the lymphatic system and demonstration that cancer can spread through it
  • The observations that suggested breast cancer development was hormone dependent

These and other discoveries enabled doctors to fine-tune breast cancer surgery. Ironically, it was surgeon Dr. Bernard Fisher’s studies in the 1980s that led to his advocacy for less surgery and limited radical mastectomy with a focus toward conserving the breast. This was a paradigm shift in breast cancer treatment.

Advancements in diagnostic techniques such as early detection by mammography and needle biopsies also helped to limit the need for radical mastectomies and to advance precision surgical procedures. And rapid advances in radiation and chemotherapy to target cancer cells as well as endocrine therapy to treat breast cancer provided strategies with and beyond breast surgery to improve outcomes.

Delivery and timing of breast cancer treatments

Newer breast cancer treatment options fall into two categories: systemic treatments that travel throughout the body, and targeted treatments that are directed toward a specific molecule or protein present on or in cancer cells that helps them thrive. Targeted therapy for breast cancer may block the action of the specific protein or disrupt associated pathways that signal to the tumor cells to keep growing.

When breast cancer treatments are administered is another consideration. Neoadjuvant therapies are systemic therapies given before primary breast cancer treatments sometimes to shrink the tumor and minimize the amount of breast tissue to be removed. In the case of inoperable breast cancer, neoadjuvant therapy can help reduce the size of a tumor so that it can be managed surgically. Adjuvant therapies are given after the primary treatment to reduce the chance of recurrence—sometimes even if there’s no evidence of residual cancer. They may be targeted or delivered systemically.

Radiation treatment

Radiation treatment, also called radiotherapy or irradiation, uses high-energy particles to kill cancer cells or slow their growth. It is used after chemotherapy or surgery to stop the growth of any cancer cells that might remain after these procedures and to reduce the risk of breast cancer recurrence in the area or in nearby lymph nodes.

Radiation treatment can also be used alone in cases where the location prohibits surgical excision or in cases of inflammatory breast cancer, an aggressive cancer that spreads via the lymph ducts.

Originally used as a systemic therapy for breast cancer, radiation treatment can now be targeted to the breast or tumor area. This approach, called external beam radiation therapy (EBRT), is currently the most commonly used method of radiation for treating breast cancer.

All radiation treatment methods do have some disadvantages, including harming nearby healthy cells, requiring multiple days or weeks of treatment before the cancer cells die, and side effects. The effects on healthy cells can be mitigated by using low doses of radiation and spreading out treatment over time. Common side effects include fatigue, skin irritation, and breast or arm swelling. In rare cases, rib fractures, chest wall tenderness, inflamed lung tissue, heart damage, or secondary cancers may develop.

While radiation therapy is generally non-invasive, doctors also employ internal radiation or brachytherapy. This procedure is done following surgery with a radiation-delivery device placed where breast tissue was removed. It provides several advantages over external beam radiation therapy. Higher doses can be used with more precision so that healthy tissue is less affected and treatment time can be shortened, which decreases side effects. BCRF investigators are exploring ways to improve radiotherapy and combat radio-resistance through several avenues, including management of side effects, increasing our understanding of breast cancer tumor biology to develop ways to make radiation more effective, and more.

Systemic therapies for breast cancer

Chemotherapy drugs

Chemotherapy is the systemic delivery (intravenously or orally) of one or more anti-cancer drugs into the body. All chemotherapy drugs work by interfering with some stage of a cancer cell’s life cycle. As such, they may prevent cell division or inhibit the cell’s ability to repair damaged DNA, both of which promote cell death. Since the hallmark of cancer is rapidly growing and dividing cells, cancer cells may be particularly vulnerable to chemotherapies. But with systemic delivery, these drugs may also affect some normal cells, which contributes to their toxicity and side effects. Typically, chemotherapy drugs are used as part of a breast cancer treatment plan that includes one or more other approaches such as surgery, radiation, endocrine therapy, and targeted therapy.

Currently, there are several classes of chemotherapy drugs FDA-approved as breast cancer treatments:

  • Anthracyclines such as doxorubicin (Adriamycin®) specifically interfere with the enzymes required to copy DNA, a process necessary for cells to divide and grow. Other anthracyclines such as epirubicin (Ellence®) damage DNA and disrupt its synthesis.
  • Cyclophosphamide (Cytoxan®) is in the nitrogen-mustard family of drugs and works by causing a strand of DNA to bind to itself or other strands. The net effect is prevention of DNA duplication which, in turn, hinders the production of RNA.
  • Fluorouracil (Adrucil®) is in the antimetabolite and pyrimidine analog families of medications. They are thought to block the action of an enzyme needed for DNA production.
  • Methotrexate (Rheumatrex®, Trexall®) is also an antimetabolite but one that blocks the synthesis of an important element of DNA. This stops cells from duplicating DNA and hinders downstream actions such as RNA synthesis and protein production.
  • Taxanes, such as paclitaxel (Taxol®), are a class of drugs that prevent microtubule scaffolding from forming within a cell, an essential process for cell division. Docetaxel (Taxotere®) is a semi-synthetic analog of paclitaxel.

Hormonal treatments

The discovery that some breast cancers rely on hormones to fuel their growth led investigators to focus on the best ways to neutralize this effect in cancer cells. Hormone receptor (HR)–positive breast cancer cells have receptors for the hormones estrogen and progesterone and are stimulated to grow by the binding of estrogen and progesterone to their respective receptors. In addition, they are responsive to hormonal or endocrine therapy, which involves manipulation of the endocrine system to disrupt the binding and stop cancer cells from growing. Hormone/endocrine treatments for breast cancer were the first targeted therapies for breast cancer, and there are currently several types being used in the clinic.

The oldest systemic hormone treatment for breast cancer and the first systemic adjuvant treatment to be tested in a clinical trial was ovarian suppression. The ovaries are the primary producers of estrogen in premenopausal women, and those with ER-positive breast cancer can benefit from ovarian suppression. Ovarian suppression drugs, a type of endocrine therapy, were developed to prevent estrogen production by the ovaries. Current drugs such as goserelin (Zoladex®) and leuprolide (Lupron®) work by disrupting signals from the brain that tell the ovaries to produce estrogen. Although they work by different mechanisms, the net effect is to switch off estrogen production.

BCRF has long supported the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) clinical studies in ovarian suppression. These studies are ongoing and will result in 10–20-year follow-up analysis.

Other hormonal breast cancer treatments for breast cancer can decrease the effect of estrogen on cancer cells’ growth by interfering with the binding of estrogen to its receptor. So far, BCRF researchers and others have devised two classes of drugs to accomplish this: selective estrogen response modulators (SERMs) and selective estrogen receptor degraders (SERDs).

SERMs bind to estrogen receptors and cause a structural change that prevents estrogen from connecting to its breast cancer cell receptors, thus keeping the cells from receiving growth signals. Tamoxifen (Nolvadex®, Soltamox®), raloxifene (Evista®), and toremifene (Fareston®) are SERMs used to stop ER-positive breast cancer from growing and spreading.

Although SERDs also bind to estrogen receptors, they work in a slightly different way. As the name implies, the interaction serves to target the receptor for destruction or degradation. Thus, SERDs prevent estrogen from having a means to signal to breast cancer cells to keep growing. Fulvestrant (Faslodex®) was the first SERD to be available for breast cancer treatment. Most recently (2023), elascestrant (Orserdu®) was FDA approved for treating postmenopausal women with ER-positive breast cancer.

BCRF investigators have also been instrumental in developing and testing other hormonal breast cancer treatments called aromatase inhibitors (AIs) that inhibit hormone synthesis. These drugs are important for treating HR-positive breast cancer in postmenopausal women whose ovaries no longer produce estrogen. Without ovarian production, the body uses other ways to produce estrogen by converting androgens (other sex hormones) into estrogens. The enzyme aromatase mediates this conversion, and aromatase inhibitor drugs were developed to stop the enzyme. The AIs anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) can lower the estrogen levels in the body and slow or stop the growth of tumor cells that require estrogen to grow. Aromatase inhibitor drugs may also be used alone or after tamoxifen treatment (see below) to lower the risk of breast cancer recurrence.  

Targeted therapies for breast cancer

PARP inhibitors

During a cell’s growth cycle, DNA damage occurs on average 60,000 times a day and efficient DNA repair is necessary for normal cell growth. Poly (ADP-ribose) polymerase (PARP) is a family of proteins known to mediate the repair of damaged DNA and serves a vital function in the cell growth cycle. A hallmark of cancer is genomic instability that often arises because rapidly dividing cancer cells cannot repair DNA efficiently.

BRCA1 and BRCA2 (discovered by BCRF investigators and their colleagues) are proteins also important for the repair of DNA. When the gene for one of these proteins is mutated, the change can lead to errors in DNA repair that can eventually cause breast cancer. Researchers postulated that these cells are more reliant on PARP to repair DNA, so perhaps PARP would be an attractive target for therapy. PARP inhibitors could potentially exacerbate the DNA repair defect in BRCA1/2 mutated cells and promote cancer cell death.

PARP inhibitors oloparib (Lynparza®) and talazoparib (Talzenna®) were developed and clinically tested in patients with BRCA1/2 mutated breast cancer. They target and trap PARP proteins on DNA to block the proteins’ normal function. This disrupts cell replication and preferentially causes cell death in cancer cells, which grow faster and accumulate damaged DNA faster than non-cancerous cells. Chemotherapy and radiotherapy also work by inducing high levels of DNA damage but may also affect healthy tissues. Targeted PARP inhibitors combined with either chemotherapy or radiation may help to increase the efficacy of these treatments and minimize the damage to normal cells.

CDK4/6 inhibitors

Cyclin-dependent kinases 4 and 6 (CDK4/6) are proteins found in healthy and cancerous cells and control how quickly cells grow and divide. Discovered by a BCRF investigator, cyclin-dependent kinases can become overactive and cause cells to grow and divide uncontrollably, including breast cancer cells. CDK4/6 inhibitors interrupt these proteins to slow or even stop the cancer cells from growing.

Several CDK4/6 inhibitors have been FDA-approved for treating HR-positive/HER2-negative metastatic breast cancer based on the studies of BCRF investigators and others.

  • Palbociclib (Ibrance®) was the first selective CDK4/6 inhibitor approved (in combination with the aromatase inhibitor letrozole).
  • Ribociclib (Kisqali®) was approved in combination with an aromatase inhibitor or the hormonal treatment fulvestrant as an initial endocrine-based therapy. It can also be used following disease progression on endocrine therapy in postmenopausal women or in men.
  • Abemaciclib (Verzenio®) is the most recent CDK4/6 inhibitor approved in combination with fulvestrant.

Monoclonal antibodies

Monoclonal antibodies are often thought of as a relatively new targeted therapy for breast cancer. But the existence of antibodies was postulated in the 1890s, and scientific observations over the last century have unmasked their potential to precisely target cancer cells. Researchers have since isolated them, identified their functions, and replicated them in the laboratory to fight cancer.

Antibodies are produced by the body as a natural defense against foreign substances, binding to them and marking them for destruction. They can also stimulate the body’s immune system to promote long-lasting responses to these substances. Monoclonal antibodies (mAbs) are produced by B cells, one component of the immune system, with a specific subset or clone of B cells selectively producing one mAb that recognizes one specific portion of a protein or antigen. Researchers have developed laboratory models to recapitulate mAb production and leveraged this technique to create mAbs that can target cancer cell antigens.

At the intersection of mAb technology and the identification of specific proteins on breast cancer cells such as HER2, Trop2, and PD-1, targeted mAbs for treating breast cancer emerged.

The HER2 protein is a receptor found on the surface of normal cells and transduces growth signals from the surface into cells. In some breast cancers, HER2 protein can be overexpressed up to 100 times more than in normal cells. The elevated levels result in the delivery of sustained signals into the cell to keep growing and can therefore lead to tumor formation. Several mAbs have been developed against HER2:

  • Trastuzumab (Herceptin®) binds HER2 protein and causes its internalization into the cancer cell thereby negating its growth signaling function. Trastuzumab was tested by BCRF investigators, and their studies led to its FDA approval as the first mAb for treating HER2-positive breast cancer either alone or in combination with chemotherapy.
  • Pertuzumab (Perjeta®) is used in combination with trastuzumab and docetaxel (a chemotherapy drug) for treating metastatic HER2-positive breast cancer or as neoadjuvant therapy for treating early HER2-positive breast cancer. It differs from trastuzumab in that it prevents HER2 from forming a dimer (two HER2 molecules bonded together). Dimerization is necessary for HER2 to transmit growth signals into the cell.
  • Margetuximab (Margenza®) is FDA approved (in combination with chemotherapy) for treating people with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Margetuximab is engineered to bind to HER2 protein as well as nearby immune cells. It has two mechanisms of action: dampening HER2 signaling to decrease cell growth or induce cell death and tagging HER2-positive tumor cells for destruction by the body’s immune system.

PD-1 receptor is an immune checkpoint protein, so called because it prevents the immune system from attacking the body’s own tissues. Present on immune cells called T-cells, it binds to the PD-L1 or PD-L2 proteins on normal cells, deactivating any potential immune response against these cells. But cancer cells also make these proteins and are therefore recognized and protected by T-cells, which allows tumor cells to evade the body’s immune system. Pembrolizumab (Keytruda®) is a mAb that binds to, and blocks PD-1 receptor protein found on immune cells. By binding to PD-1 receptors, pembrolizumab prevents tumor cells from hiding from the immune system and allows the immune system to recognize, target, and destroy these cancer cells.

Antibody-drug conjugates

Antibody drug conjugates (ADCs) are a relatively new class of targeted therapy for breast cancer that are engineered to deliver drugs to cancer cells with substantially less toxicity to surrounding normal cells. ADCs are composed of three parts: an antibody, a drug or payload, and a dissolvable linker that connects the antibody to the drug. They are powerful tools that leverage the specificity of an antibody and strategic release of a potent drug directly to the tumor cell site.

Although ADC technology has been around for decades, ADCs have only recently been FDA approved for treating breast cancer including metastatic, HER2-positive breast cancer and recently, triple-negative breast cancer. They include:

  • Ado-trastuzumab emtansine (T-DM1/Kadcyla®) is composed of the antibody trastuzumab linked to the chemotherapy drug (payload) emtansine that disrupts microtubule-mediated cell division and prevents targeted tumor cells from growing.
  • Trastuzumab deruxtecan (T-DXd/Enhertu®) also contains trastuzumab, but here the antibody is linked to a different drug, deruxtecan, a topoisomerase 1 inhibitor that blocks tumor cells’ DNA repair ability. Interestingly, T-DXd has demonstrated efficacy in brain metastases, meaning that it can permeate the blood brain barrier, which is unexpected given that ADCs are typically large constructs. T-DXd is also effective in HER2-low breast cancers (55 percent of all cancers), a finding that resulted in practice-changing treatment for these patients.
  • Sacituzumab govitecan (SG/Trodelvy®) includes the antibody sacituzumab that targets TROP-2 protein found on all subtypes of breast cancer cells, linked to SN-38, another more potent topoisomerase 1 inhibitor. It is FDA-approved for triple-negative breast cancer treatment, a subtype that has few targeted treatment options. And more recently, sacituzumab govitecan was FDA-approved for treating HR-positive, HER2-negative breast cancer.

At this point, there are 17 ADCs in clinical trials. Nine HER2-directed ADCs are being tested in combination with novel payloads, and eight ADCs are being studied in combination with novel antibody targets.

Tyrosine kinase inhibitors

Tyrosine kinases are part of a family of enzymes that transfer a phosphate group to specific proteins in a cell. Phosphorylation of proteins is a mechanism used by cells to communicate signals that mediate certain cell processes such as growth and division. The HER2 protein contains a tyrosine kinase domain that is involved in cell growth and provided an attractive target for development of drugs called tyrosine kinase inhibitors (TKIs). These small molecule inhibitors bind to the tyrosine kinase domain of HER2 and halt activation of the cell signaling pathway.

Three tyrosine kinase inhibitors have been FDA-approved as HER2-positive breast cancer treatments: tucatinib (Tukysa®), lapatinib (Tykerb® or Tyverb®), and neratinib (Nerlynx®). BCRF investigator–led studies showed that tucatinib is the first TKI to demonstrate clinical efficacy in breast cancer with brain metastases, presumably because these small molecules can cross the blood-brain barrier.

PI3K/AKT/mTOR pathway inhibitors

There are several signaling pathways also used by cells to relay messages important for cell functions. The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is one. In approximately 30–40 percent of HR-positive/HER2-negative breast cancer cases, genetic abnormalities in the pathway’s components can lead to its activation, sustained cell growth, and tumor formation.

One such genetic aberration was discovered in PI3K, the PIK3CA gene. Endocrine therapy is the standard treatment for patients with HR-positive/HER2-negative advanced breast cancer. However, resistance to endocrine-based therapy can occur. The connection between mutations in the PIK3CA gene and overactivation of PI3K led researchers to suspect that PI3K inhibitors could cancel the effects of the mutations and possibly provide a way to overcome endocrine therapy resistance. The PI3K inhibitor alpelisib (PIQRAY®) was developed and clinically tested in trials led by BCRF-investigators. These trials were instrumental in its FDA approval in combination with fulvestrant to treat PIK3CA-mutated, HR-positive/HER2-negative breast cancers that had prior endocrine therapy.

Another key component of the PI3K/AKT/mTOR pathway is the serine/threonine kinase AKT, which exerts a pivotal role in cell growth, proliferation, survival, and metabolism. Targeting AKT is an attractive treatment option for many breast cancers, particularly those resistant to conventional breast cancer treatments. In 2023, a first-in-class AKT inhibitor called capivasertib (TRUQAP™) was FDA approved for treating HR-positive/HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine-based regimen.

On the horizon

Scientists are constantly making advances in breast cancer treatments. Several new drugs and strategies are under investigation, including additional endocrine therapies, mAbs, and ADCs, uncovering new targets for treatment and leveraging new technologies such as bi-specific antibodies—all built on previous discoveries made over decades and indeed centuries. Researchers are also exploring new combinations of existing treatments and working to optimize dosing strategies with patients in mind—balancing the efficacy of treatments with side effects.

BCRF investigators have led the way in developing and testing of recent breast cancer treatment strategies. As the pace of discovery and advancements in research and technology are accelerating, they will no doubt be instrumental in fine-tuning breast cancer treatments with more and more precise options. BCRF is committed to supporting efforts to move us closer to the promise of precision medicine—therapies tailored to an individual’s tumor characteristics, and expanding breast cancer treatment options.

References:

Beatson, G. T. (1983). On The Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases. CA: A Cancer Journal for Clinicians, 33(2), 108–121. https://doi.org/10.3322/canjclin.33.2.108

Drugs approved for breast cancer. (2023, December 20). National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/breast

Lakhtakia, R. (2014). A Brief History of Breast Cancer: Part I: Surgical domination reinvented. DOAJ (DOAJ: Directory of Open Access Journals). https://doaj.org/article/70d9ab7b41354b46a0cb103edfd602be

Swain, S. M., Shastry, M., & Hamilton, E. (2022). Targeting HER2-positive breast cancer: advances and future directions. Nature Reviews Drug Discovery, 22(2), 101–126. https://doi.org/10.1038/s41573-022-00579-0

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BCRF-Supported Trial Shows Lifestyle Interventions May Improve Breast Cancer Outcomes https://www.bcrf.org/bcrf-supported-trial-shows-lifestyle-interventions-may-improve-breast-cancer-outcomes/ Tue, 05 Mar 2024 14:25:00 +0000 https://www.bcrf.org/?p=26483 Study highlights the impact of adopting a healthy diet and exercise regimen early after diagnosis

In the last decade, breast cancer death rates have decreased by one percent each year, in part due to advances in breast cancer treatments, including chemotherapy. While lifesaving, chemotherapy can come with adverse side effects, such as fatigue, nausea, and vomiting, and as a result, patients do not always complete the full course of treatment. Finding ways to make chemotherapy more tolerable for patients who need it and identifying the right patients to receive it are key areas of research in the field.

In a recent study published in the Journal of Clinical Oncology, BCRF investigator Dr. Melinda Irwin reported the results of the LEANer clinical trial showing that lifestyle interventions can potentially improve a patient’s outcomes and quality of life after chemotherapy.

What were the goals of the study?

The LEANer study (Lifestyle, Exercise, and Nutrition Study Early After Diagnosis) was designed to determine how adoption of a healthy diet and exercise intervention early after diagnosis impacts chemotherapy completion. The study also evaluated if the intervention improves pathological complete response (pCR, defined as no residual invasive disease noted in the patient’s pathology report) in women after they completed pre-surgical chemotherapy (neoadjuvant therapy).

How prior LEAN study informed methods of intervention in LEANer

The research team studied 173 women with stage 1-3 breast cancer who were randomly assigned to an intervention group or a standard-of-care group. The intervention group was provided counseling sessions on nutrition and exercise, based on the protocol established in the LEAN study, which was also funded in part by BCRF. In that study, the intervention group participated in counseling sessions that promoted weight loss through both physical activity and achieving or maintaining a healthy diet.

Counseling sessions were conducted over the course of one year and led by registered dietitians (RDs) who were certified specialists in oncology nutrition with additional training in exercise science. They promoted a predominantly plant-based diet, with less than or equal to 18 ounces of red meat per week, and the following daily guidelines:

  • a combination of at least five fruits and/or vegetable servings
  • 25 grams or more of fiber
  • less than 30 grams of added sugar
  • no more than one alcoholic beverage  
  • limited processed foods

A physical activity program was also incorporated into the 30-minute counseling sessions where RDs coached participants on a home-based exercise regimen. The participants were encouraged to engage in 150 minutes or more per week of moderate to vigorous physical activity or 75 minutes per week of vigorous physical activity plus twice-weekly resistance training.

How did the intervention impact study participants?

Participants in the intervention group increased their intake of fruit, vegetables, and fiber during chemotherapy and reported spending more time exercising and strength training than women in the standard-of-care group. Interestingly, the researchers observed that both groups completed chemotherapy doses at very high rates, as measured by the ratio of chemotherapy delivered to the chemotherapy dose prescribed (relative dose intensity, or RDI). The RDI was 93 percent for both groups; an RDI below 85 percent is a common clinical threshold associated with worse chemotherapy effectiveness. This was a surprising finding given that more than 25 percent of patients in observational studies experience a low RDI and are not able to complete prescribed chemotherapy regimens.

However, researchers found that the diet and exercise intervention evaluated in this study was associated with a greater pathological complete response (pCR) in patients with hormone receptor (HR)–positive/HER2-negative and triple-negative breast cancer undergoing presurgical chemotherapy.

Although the mechanisms driving higher pCR rates in the intervention group (53 percent compared to 28 percent in the standard-of-care group) require further investigation, it’s possible that by improving their diets and exercising more, patients experienced reduced inflammation and enhanced immune response.

“That almost twice as many women randomized to the exercise and nutrition intervention during neoadjuvant chemotherapy had no evidence of breast cancer at the time of surgery compared to women randomized to usual care during neoadjuvant chemotherapy was a clinically important finding—yet could be a chance finding as our study was not designed to answer this question as a primary aim,” Dr. Irwin said. “With BCRF funding, we are now initiating a trial in women with triple-negative breast cancer receiving neoadjuvant chemotherapy to specifically answer this question: Does exercising and adopting a high-quality diet during chemotherapy improve pathologic complete response?”

What this means for patients

Adverse side effects of chemotherapy are often so serious that patients or their doctors will discontinue chemotherapy treatments altogether, but reducing chemotherapy doses can have serious consequences. With this study, Dr. Irwin and her research team sought to find lifestyle changes that could give patients better tools for managing side effects, improve their quality of life during treatment, and encourage chemotherapy adherence. The nutrition and exercise interventions in this study specifically address many of the common side effects associated with chemotherapy.

The research team will further investigate how this intervention improves adherence to endocrine therapy and prevents common treatment side effects such as peripheral neuropathy, arthralgia (i.e., joint pain), and cognitive function.  Previous studies have examined how to treat those symptoms after they have occurred, but the LEANer study is one of the first trials to examine if diet and exercise can prevent these common chemotherapy side effects.

The study team is also planning additional investigation into the potential mechanisms behind the increased pCR rates in the intervention group. This finding is particularly exciting as it highlights the role nonpharmaceutical interventions can play in a breast cancer treatment plan and, indeed, these interventions warrant further study.

References:

Anderson, C., Harrigan, M., George, S. M., Ferrucci, L. M., Sanft, T., Irwin, M. L., & Cartmel, B. (2016). Changes in diet quality in a randomized weight loss trial in breast cancer survivors: the lifestyle, exercise, and nutrition (LEAN) study. Npj Breast Cancer, 2(1). https://doi.org/10.1038/npjbcancer.2016.26

Sanft, T., Harrigan, M., McGowan, C., Cartmel, B., Zupa, M., Li, F., Ferrucci, L. M., Puklin, L., Cao, A., Nguyen, T. H., Neuhouser, M. L., Hershman, D. L., Basen-Engquist, K., Jones, B. A., Knobf, T., Chagpar, A. B., Silber, A., Tanasijevic, A., Ligibel, J. A., & Irwin, M. L. (2023). Randomized Trial of Exercise and Nutrition on chemotherapy completion and pathologic complete response in women with breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study. Journal of Clinical Oncology, 41(34), 5285–5295. https://doi.org/10.1200/jco.23.00871

Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), 17–48. https://doi.org/10.3322/caac.21763

Vavra, K., Saadeh, C., Rosen, A. L., Uptigrove, C. E., & Srkalović, G. (2013). Improving the relative dose intensity of systemic chemotherapy in a Community-Based Outpatient Cancer Center. Journal of Oncology Practice, 9(5), e203–e211. https://doi.org/10.1200/jop.2012.000810

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Research Is the Reason I Can Cross the Finish Line https://www.bcrf.org/research-is-the-reason-2023-triple-negative-breast-cancer-madeline/ Tue, 27 Feb 2024 15:32:21 +0000 https://www.bcrf.org/?p=26442 After being diagnosed with triple-negative breast cancer in her 20s, Madeline credits research for getting her back to health so she could complete her fifth marathon

In January 2020, while finishing graduate school in London, Madeline McCloughan found a lump in her left breast. Alarmed by this discovery, she visited her doctor, who told her to keep an eye on it. After a month, when it didn’t go away, she went in for an ultrasound and breast biopsy.

“That was over the course of three appointments, and then it was March 2020,” she remembered. “It looked like the U.S. was going to shut its borders, so I made the decision to come back and finish my degree remotely.”

On March 15, 2020, Madeline made it back to her hometown of St. Paul, Minnesota, and two days later, she received a phone call from her doctor back in London.

“He shared my test results that showed it was cancer,” she said. “I was alone when I found out, and it was like an out-of-body experience.”

Madeline soon found out she had stage 3, triple-negative breast cancer (TNBC), an aggressive form of the disease that disproportionately impacts younger women and lacks many targeted treatments—making it a major focus of BCRF’s annual research investment.

“There weren’t any women close to me that I knew that had breast cancer,” she said. “I never thought it was something that happened to people in their 20s, and I wasn’t aware of that subtype either.”

Right as she was about to start chemotherapy, Madeline developed a slight fever. Since she had traveled recently, her doctor tested her for COVID-19. The test came back positive, delaying treatment for nearly two weeks so she could quarantine.

“Having COVID at the beginning, when there were still a lot of unknowns, was tough,” she said. “The first few weeks after your diagnosis are probably when you need a hug the most.”

In the end, Madeline completed several months of chemotherapy, had a double mastectomy, and finished 28 rounds of radiation right before the end of 2020. Because of the pandemic, Madeline was forced to undergo most of these treatments alone.

Surgery, of all her treatments, was the hardest part of her cancer experience.

“I wasn’t mentally prepared for the impact of surgery. I didn’t have a reference point in the same way that I did for chemotherapy since people talk about it much more,” she said.

Now that treatment is behind her, Madeline is grateful to have had a complete response to treatment but still navigating the complex survivorship experience.

“Life post-treatment is like a roller coaster,” she said. “It’s an excellent lesson in giving yourself grace. Sometimes things go really well, and sometimes things are hard. But I think it’s gotten easier with time.”

Running has always been one of Madeline’s passions, and prior to her cancer diagnosis, she had completed four marathons and was training for her fifth. She was thrilled to be able to start training again.

“Running is central to my identity, and I told my oncologist at my first appointment that I’m going to run a marathon when all this is over,” she said.

To cross the finish line of that fifth marathon and celebrate putting breast cancer behind her, she invited friends and family to join her in running the 2021 Twin Cities Marathon on Team BCRF.

“It was so special to have all my loved ones get together and run to raise money for BCRF,” she said.

Madeline alone raised an incredible $21,791 for breast cancer research—more than she ever expected—and her friends and family’s support helped push the entire Twin Cities team to raise more than $52,000 total. It made crossing the finish line that much more gratifying.

Madeline’s experience with breast cancer also showed her the importance of research firsthand. She credits it for the fact that her chemotherapy regimen was shorter and that she was offered more treatment options. Because of its aggressiveness and fewer available therapies, TNBC especially needs more research, Madeline said.

“We need research to come up with treatment options,” she said. “I benefitted from the women before me who went through studies and trials, and so I want to do what I can to pay it forward.”

Read more stories from BCRF’s Research Is the Reason storytelling initiative here.
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The Breast Cancer Research Foundation Names Karen Hale New Board Co-chair https://www.bcrf.org/2024-bcrf-announces-new-board-co-chair/ Tue, 27 Feb 2024 13:31:25 +0000 https://www.bcrf.org/?p=26395 Hale to serve alongside William P. Lauder in leading the Foundation’s Board of Directors

FEBRUARY 26, 2024 – Karen Hale, a member of the Breast Cancer Research Foundation (BCRF) Board of Directors since 2018, has been named co-chair and is poised to lead the organization—the largest private funder of breast cancer research in the world—as it marks three decades of progress in breast cancer prevention and care. Succeeding Kinga Lampert, who served in the role for 10 years, Hale officially takes the helm as of February 26, 2024 alongside BCRF Board Co-chair William P. Lauder, Executive Chairman of The Estée Lauder Companies Inc.

This year alone, BCRF is funding $60.2 million in grants to more than 250 scientists at leading medical and academic institutions across 15 countries.

“Even as BCRF marks 30 years of advancing every major breakthrough in breast cancer research, we remain steadfast in our mission to ultimately eradicate the disease and end its life-threatening power,” said BCRF President and CEO Donna McKay. “We know Karen’s increased leadership will be invaluable to our forward momentum. I have no doubt that, with Karen and William driving the philanthropic and strategic vision of BCRF, we will absolutely speed the delivery of better treatment options and improve our ability to prevent the disease entirely for the millions of patients around the world that are depending on us.”

Stepping into the role of BCRF’s Board co-chair, Hale continues to exemplify one of the deepest tenets of philanthropy: supporting mission-driven organizations with a meaningful track record of genuine impact.

Hale and her husband, Rob, are among the most preeminent philanthropists in the country with a wide, diverse range of giving, all with the goal of advancing mission-based organizations. With a long history of supporting premier medical research institutions including Boston Children’s Hospital, Brigham and Women’s Hospital, and the Dana-Farber Cancer Institute, and funding dozens of community-based nonprofit organizations, the Hales have been quietly advancing missions as broad as curing cancer and as specific as programs to help disadvantaged youth through lacrosse.

BCRF holds a special meaning for Hale: Her mother has been living with metastatic disease for the last 4 years, nearly 20 years after being initially treated for breast cancer. Hale credits the targeted therapy Herceptin, made possible by BCRF-funded research, for extending her mother’s life.

“Our mission is not just important to me but is a matter of improving public health and our impact is truly global in scope. I have spent years working with the Breast Cancer Research Foundation, especially in our fundraising efforts in the New England region. My unique lens as a member of the Board of Directors has given me the opportunity to witness the brilliance and direct impact of BCRF’s funding and the organization’s unparalleled commitment to eradicating breast cancer,” said Hale.” I am deeply grateful for the faith the Board has shown in electing me to this position and I look forward to working more closely with William as co-chair and the entire BCRF team.”

Breast cancer research is at a critical inflection point as incidence is on the rise, health inequities remain gravely stark, and metastatic disease continues to take lives. And yet, the power of research remains evident: improvements in treatment and screening have resulted in a 43% percent decline in deaths over the last three decades since BCRF’s founding.

“I am honored to welcome Karen to join me as co-chair of BCRF.  I have deep respect and admiration for her longstanding commitment to elevating and funding lifesaving research.  I look forward to partnering with Karen to help prevent and cure breast cancer,” said William P. Lauder.

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About the Breast Cancer Research Foundation

Breast cancer is a complex disease with no simple solution. Research is the key to stopping it in its tracks. Founded in 1993 by Evelyn H. Lauder, the Breast Cancer Research Foundation is the largest private funder of breast cancer research in the world. We invest in the best minds in science—from those investigating prevention to metastasis—and foster cross-disciplinary collaboration. Our approach accelerates the entire field and moves us closer to the answers we urgently need. We can’t stop now. Join us in fueling the world’s most promising research. With you, we will be the end of breast cancer. Learn more and get involved at BCRF.org.

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Improving Breast Cancer Radiation Treatments with Dr. Rachel Jimenez https://www.bcrf.org/2024-podcast-dr-rachel-jimenez-radiation-breast-cancer/ Thu, 29 Feb 2024 15:10:21 +0000 https://www.bcrf.org/?p=26421 Dr. Jimenez discusses a new strategy for delivering radiation that could reduce treatment time and minimize its damaging effects on the heart

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.


Read the transcript below: 

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.

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BCRF Mourns Loss of Investigator Dr. Allen Tannenbaum https://www.bcrf.org/bcrf-mourns-loss-of-investigator-dr-allen-tannenbaum/ Tue, 20 Feb 2024 17:19:31 +0000 https://www.bcrf.org/?p=26323 The scientific community has lost a pioneering mathematician

It is with great sadness that BCRF shares the news of the passing of Dr. Allen Tannenbaum, a true giant in the fields of applied mathematics and computer science.

A BCRF investigator since 2017, Dr. Tannenbaum’s career spanned decades across many specialties, including biomedical imaging and bioinformatics. His work with fellow BCRF investigator Dr. Joseph Deasy, supported by the Simons Foundation, was focused on the emerging field of mathematical oncology: leveraging mathematical approaches to fight cancer. Dr. Tannenbaum envisioned a way to connect and correlate cancer’s many complex networks and interrelated facets.

In partnership with Dr. Deasy, he worked to gain insight into how complex, interacting systems drive the disease, and they sought to better understand tumorigenesis, identify new targets for treatment, refine breast cancer molecular subtypes, and ultimately move precision medicine for cancer forward.

BCRF’s Founding Scientific Director Dr. Larry Norton was a longtime collaborator of Dr. Tannenbaum’s.

“Allen was a true luminary, not only in the sense of recognition by his peers but by his casting light on the mysteries of biology and medicine that have long puzzled the best minds,” Dr. Norton said. “He did this through a unique confluence of talents, including his abilities to interpret difficult biology in sophisticated mathematical terms and work with and inspire others. To say that he’ll be missed is an understatement beyond measure.”

At the time of his passing, Dr. Tannenbaum was the Distinguished Professor of Computer Science and Applied Mathematics & Statistics at Stony Brook University. He authored numerous publications, which were well received and cited more than 36,000 times by his peers. He was also the recipient of many awards, including the Kennedy Research Prize, the  National Science Foundation Research Initiation Award, and the O. Hugo Schuck Award.

BCRF extends its sympathies to Dr. Tannenbaum’s family, friends, and colleagues in this time of sorrow.

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BCRF’s Precision Prevention Initiative to Support 8 Innovative New Projects https://www.bcrf.org/bcrf-precision-prevention-initiative-new-projects-2024/ Wed, 21 Feb 2024 17:52:33 +0000 https://www.bcrf.org/?p=26326

Investigators aim to personalize breast cancer prevention and save lives

Globally, breast cancer is the most frequently diagnosed cancer in women, affecting an estimated 2.3 million annually. In the U.S., where breast cancer has been the most frequently diagnosed cancer in women for many years, the American Cancer Society estimates that there will be over 310,000 new cases of breast cancer and more than 42,000 deaths in 2024 alone. With incidences rising, preventing and intercepting breast cancer is more important than ever.

BCRF is committed to supporting prevention research that takes a personalized approach and, launched its Precision Prevention Initiative (PPI) in 2019. Now, building on the great success of the first set of projects, BCRF is embarking on PPI’s next phase to support more bold and innovative research. Our goal: to harness the incredible power of precision medicine for prevention—tailoring strategies based on an individual’s genetics, environment, and lifestyle—and stop breast cancer before it starts.

The promise of prevention

Research has shown that breast cancer risk may be reduced by maintaining a healthy weight and avoiding weight gain; exercising; eating more fruits, vegetables, and whole grains; cutting down on meat and processed foods; limiting alcohol; and quitting smoking. However, more research is needed to truly personalize and advance prevention strategies.  

BCRF supports a wide range of related research through its annual grants program, providing sustained funding for approximately 40 projects every year, including the most promising research from the first phase of PPI. Our investigators are discovering innovative approaches to breast cancer prevention across three core pillars: assessing risk, devising risk-reducing interventions, and improving early detection. Phase two of PPI accelerates this essential research.

This initiative pursues a better understanding and assessment of breast cancer risk, well beyond inherited gene mutations in high-risk genetic susceptibility genes like BRCA1 and BRCA2, and beyond family and personal history. With a more complete picture of risk factors, researchers can give patients a more accurate personalized risk score that estimates a woman’s chance of developing breast cancer. To date, PPI-funded research has revealed genomic factors that drive progression of premalignancies to triple-negative breast cancer (TNBC) and has identified novel targets and tested drugs that block the early development of breast cancer.

Early detection improves outcomes, and researchers are seizing the opportunity to improve strategies to find breast cancer even sooner. Work from phase one of PPI has successfully used artificial intelligence (AI) to uncover hidden clues in mammograms. They also determined that AI—in combination with extensive patient data—enables clinicians to not only detect breast cancer sooner but assess future risk. This will, ultimately, help personalize effective prevention strategies. Other work leveraged state-of-the-art imaging, AI, and machine learning to identify features of breast tissue that are associated with TNBC. Researchers then used this information to develop a TNBC-specific risk score.

Building on phase one’s success

BCRF recently launched the next phase of PPI with a three-year, $10.75 million investment to support research that will once again fuel innovation and accelerate prevention. Broadly, PPI seeks to bring the impact precision treatment has had on outcomes to the prevention arena. It challenges the research community to explore multi-disciplinary approaches to answer breast cancer’s most pressing questions in less time, use novel technologies and identify new ways of examining available data, and build infrastructure, resources, and tools that will facilitate discovery for years to come.

Specifically, phase two of PPI will focus on several areas:

  • Risk assessment and stratification to inform individualized prevention and care strategies
  • Biomarkers for determining individual risk and screening schedules to prevent the disease, detect it earlier, or predict prognosis
  • Preventative interventions that go beyond prophylactic surgery

BCRF called for researchers to think outside of the box by engaging collaborators from diverse disciplines and using areas of expertise and methodologies not normally associated with prevention or cancer research. BCRF received a range of proposals—including single-investigator innovation projects to collaborative pre-clinical, translational, clinical, and intervention studies—all with the aim of preventing breast cancer in the first place.                

PPI Phase two projects

BCRF awarded four Clinical Trial or Intervention Study Grants geared toward preventing breast cancer or evaluating the effects of interventions on health-related biomedical or behavioral outcomes:

  • Dr. Andrea De Censi is testing various strategies to improvebreast cancer chemoprevention. He will build on prior studies that show dosing schedules for tamoxifen and exemestane could be shifted with comparable efficacy and without increasing side effects. He is now determining if further improvements in quality of life can be made with every-other-day tamoxifen or every-other-day exemestane.This study will open across seven clinical sites globally. Dr. De Censi anticipates that the results of the study will inform new approaches to breast cancer prevention that are better tolerated and have potential for broader uptake and impact.
  • Dr. Olivera J. Finn is bringing the immense power of vaccines into the prevention space. The idea is that vaccines for cancer prevention will prepare the immune system to see tumor antigens on a developing tumor and destroy it. Dr. Finn has been testing one such vaccine and will conduct a clinical trial to test its safety and efficacy in women diagnosed with pre-cancerous lesions prior to surgery. If the vaccine proves effective at preventing invasive breast cancer, it may provide an exciting new approach to breast cancer prevention that could replace surgery and chemotherapy.
  • In addition to her ongoing BCRF project, Dr. Seema Khan is testing personalized dosing of tamoxifen to prevent breast cancer. Her study builds on data from previous trials showing that low-dose tamoxifen is also effective for cancer prevention and that it reduces breast density, increasing the risk reduction benefit in women with dense breasts. Dr. Khan and her team will use “mammographic dense area reduction” (DAR) as an indicator of tamoxifen response. Two hundred high-risk premenopausal women will take low-dose tamoxifen and have DAR results assessed at six and 12 months. Depending on the DAR results at these time points, participants will have the option to increase the dose and continue treatment with their optimal dose for a total of 18 months. This trial will provide the first proof-of-concept for personalized dosing in cancer prevention.
  • Dr. Darren Mays is creating a counter-marketing intervention to reduce alcohol use in young women and measure its effects on alcohol use behavior and breast cancer risk beliefs. He and his team will use several tools, including AI, to create intervention content. This content will be used in a randomized clinical trial to test if it is effective for changing young women’s beliefs about breast cancer risks from alcohol use and their alcohol use behavior. Daily data, including information about participants’ alcohol use, will be collected through phones and wearable sensors. These projects stand to advance breast cancer prevention science in a bold new way.

Two Pre-Clinical Grants showing a clear path from the bench to bedside were funded, and both are poised to advance primary breast cancer prevention by integrating advanced technologies or experimental systems:

  • In addition to his ongoing BCRF research, Dr. Jack Cuzick is assessing the utility of measuring blood hormone levels to predict which women are at high risk of breast cancer and which will benefit from risk-reducing anti-estrogen drugs. Dr. Cuzick and his team will measure hormone levels in over 100,000 women at average and high risk of breast cancer and those with ductal carcinoma in situ (DCIS), a non-invasive breast cancer that may progress to invasive breast cancer. The team will determine whether blood hormone levels correlate with the participants’ risk profiles and observed outcomes.
  • Dr. Jennifer Ligibel is investigating the link between exercise, irisin, and breast cancer development. Her team has demonstrated that irisin, a substance released by muscle during exercise, slows breast cancer development. Her team will test whether exposure to irisin leads to activation of the immune system. Then, they will conduct a clinical trial in women at increased risk of breast cancer to assess levels of circulating irisin before and after a 12-week exercise program. They will evaluate the impact of exercise on circulating irisin, as well as on immune and proliferative markers. Dr. Ligibel’s projects will help to determine the mechanisms through which exercise could reduce breast cancer risk and perhaps identify new targets for drug development to prevent breast cancer.

Two Innovation Grants were awarded to investigators seeking to expand into a new area of discovery or to address an unmet need in primary breast cancer prevention. These projects demonstrated a high likelihood of moving to the translational stage:

  • Dr. Camila dos Santos is leveraging pregnancy-associated changes in breast tissue to reduce risk. Pregnancy is correlated with a decrease in breast cancer incidence. Dr. Dos Santos has found that the post-pregnancy mammary tissue has increased numbers of specific immune cells (NKT cells) and probiotics have an established role in stimulating NKT cells. Therefore, Dr. dos Santos is investigating a possible connection between milk-associated probiotics, the control of mammary NKT cells, and tumorigenesis. NKT cells influence other immune cells that, in turn, may provide a source of local vaccination associated with pregnancy-induced breast cancer protection. Dr. dos Santos is delving into this possibility as a novel breast cancer prevention strategy.
  • Dr. Alvaro Monteiro is identifying and stratifying BRCA1 and BRCA2 gene variants that confer intermediate risk of breast cancer. Dr. Monteiro will identify gene variants of intermediate risk that can be used as a point of comparison to integrate clinical and functional data for gene variant classification and risk assessment. His objective is to formally define a new category of intermediate-risk BRCA variants and delineate the spectrum of risk in variants of breast cancer susceptibility genes to, ultimately, propose clinical guidelines that improve risk-appropriate cancer prevention.

Data generated through PPI is expected to be made available to the research community to the fullest extent possible via BCRF’s Global Data Hub.

Cancer prevention is evolving quickly as emerging technologies are incorporated into all areas of precision medicine research. BCRF has long been at the vanguard of breast cancer research. Indeed, our researchers are today’s leaders in precision prevention and will continue to drive the groundbreaking advances of the future.

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