Researchers in New England—which has the second-highest concentration of BCRF’s grantees—discuss the latest in breast cancer research

BCRF’s annual Boston Hot Pink Luncheon and Symposium convenes the Foundation’s dedicated New England–based supporters to honor the area’s investigators and raise additional funds for lifesaving breast cancer research.

This year’s virtual program included an outstanding expert panel of BCRF investigators, who discussed novel breast cancer therapies and what’s on the horizon in research.

The panel was moderated by BCRF Scientific Director Dr. Judy Garber of Dana-Farber Cancer Institute and Harvard Medical School. The symposium panelists included:

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


Read the transcript below: 

Dr. Judy Garber: Hello everyone and thank you for joining us today. At BCRF, we encourage researchers from different scientific disciplines to collaborate. To think outside the box together, explore new theories, and follow promising leads that bring us closer to our ultimate goal: cures for breast cancer and preventing it altogether.

Today's panel of BCRF funded investigators from New England is a very multidisciplinary group. And we're going to talk about how research in these areas is changing the future of the care.

So first I'm going to ask everyone to introduce him or herself. And then we'll get down to some questions. Dr. Irwin is with us from Yale. Will you talk about, tell us a little bit about yourself and your BCRF funded work?

Dr. Melinda Irwin:  Yes, happy to. Thank you for inviting me to participate today. So I am a Professor of Epidemiology at the Yale School of Public Health. And I'm also the Associate Director for Population Sciences in the Yale Cancer Center.

So my research, broadly speaking, focuses on cancer prevention and control and the role of lifestyle factors such as weight, exercise and diet and how it might prevent or control breast cancer.

Dr. Judy Garber: Thank you, Melinda. Beth Mittendorf is with us here in Boston at Dana-Farber. Dr. Mittendorf?

Dr. Elizabeth Mittendorf: Thanks, Judy and thanks to BCRF for inviting me to participate. So I am a breast surgical oncologist. But my research focus has largely been in breast tumor immunology. I've been long interested in how the immune system recognizes and responds to breast cancer. And I'm confident we're going to be talking a bit about immunotherapy today and that's really been the focus of my BCRF-funded work. Trying to identify factors that would predict who's going to respond from that form of treatment.

Dr. Judy Garber: Thank you. And last, but hardly least, Dr. Dennis Sgroi from the Massachusetts General Hospital. Dennis?

Dr. Dennis Sgroi: Thank you very much for the opportunity to speak today. I am a breast pathologist. I'm a Professor of Breast Pathology at Harvard Medical School and here at the Massachusetts General Hospital. My research has really focused on trying to identify biomarkers that are both a prognostic. Or in other words, they will predict for risk of recurrence as well as predicting for treatment behavior.

And in particular, we have worked on a biomarker that helps patients, especially ER-positive breast cancer patients make decisions about their hormonal therapy.

Dr. Judy Garber: Great. So as you can hear, we have quite a diverse group of researchers. And first, we want to hear a little bit about their areas of work where there's so much activity and so much excitement. So Dr. Irwin, let's start with you. Talk a little bit for us, please, about how weight and exercise and play a role in risk of getting breast cancer. And what do they also have to do with the long-term outcome?

Dr. Melinda Irwin: So for a couple of decades now, we have known from observational research that a higher weight or a higher body mass index and lower physical activity levels and poor diet quality are associated with an increased risk of developing breast cancer, as well as having a recurrence or dying of breast cancer.

It's not till the past 10 or 20 years or so that we've really been doing randomized controlled trials to isolate or better understand the mechanisms of how these modifiable lifestyle behaviors impact risk of developing or dying of breast cancer.

And so fortunately with Breast Cancer Research Foundation funds, I have been able to conduct a randomized trial of women diagnosed with breast cancer and receiving chemotherapy. And then examining a nutrition and exercise intervention and how that might improve various biobehavioral outcomes related to breast cancer.

Markers measured in the blood, in the tissue, as well as treatment-related toxicity and treatment adherence and other patient reported outcomes. So that we can really better understand what type of diet and what amount of exercise is most important for preventing and treating breast cancer.

And so far, I think two takeaway really important messages are that we know is reducing sedentary time. We don't have to run a marathon, but reducing our sedentary time because we've become so inactive because of iPhones and other advances is a really good thing, as well as preventing weight gain as we age.

Dr. Judy Garber: Beth, you've been really at the forefront of some of the most immunology discoveries. Can you talk to us a little about how we can harness the immune system to try to fight breast cancer?

Dr. Elizabeth Mittendorf: Yes, thanks, Judy. The last couple of years have been really been important for immunotherapy and breast cancer because we now have clinical trials that have shown that for our patients specifically with triple-negative breast cancer, if we give them drugs called immune checkpoint blockade, and there's a number of different flavors. But the one that's approved for us is Pembrolizumab.

If we give those to patients, it improves their response to treatment, so we give it in combination with chemotherapy. And so, what we know is that for patients with metastatic triple-negative breast cancer, if we are to give them this Pembrolizumab along with chemotherapy, it really augments the immune response such that they have improved survival, meaning longer time until they progress or would need to change their treatments.

I think one of the things that's been really exciting just in the last couple of months is the trial data looking at that same drug, but now given in the very earliest stages, earlier stages of disease. So, our patients with stage 2 or 3 triple-negative breast cancer that's operable.

So, what we're finding is that if we give them Pembrolizumab with their chemotherapy before surgery, when I, as a surgeon, take them to the operating room, it's much more likely that the pathologist such as Dennis will come back and say, "There's no tumor left."

And that's important. It's an improvement in what we call the pathologic complete response. But even more important, the longer-term follow-up for that trial showed that those patients have improved event-free survival. Meaning it's also less likely that the cancer's coming back.

And so, with these two approvals immunotherapy finally is a somewhat form of targeted therapy for triple-negative breast cancer, which we know for so long has been a need in our field to find something other than just chemotherapy for those patients. So it's been a very good couple of years to advance immunotherapy in our armamentarium.

Dr. Judy Garber: That is really such progress to say that we always wondered how could you develop breast cancer? Where was the immune system? And you've been able to basically turn it back on at the right time and try to bring it back into the battle.

And now just in investigational times but in actually parts of treatment for everybody. So it's not something you want to add years later. If you had triple-negative breast cancer years ago, it's probably not coming back. But for patients now starting out, we can really make treatment better. So thank you, Beth.

Dr. Elizabeth Mittendorf: Yes, yes. Well, that's such an important point that you make though, Judy, of when to give these agents. And then I mentioned that it's approved in both the metastatic setting, as well as the early disease setting, I think those of us who are really interested in tumor immunology recognize that it may be working by different mechanisms in those two settings.

And so again, a big thanks and shout out to the BCRF for giving us the opportunity to try to collect tissues from our patients who are now getting these agents as standard treatment to better investigate them.

So, we have a real opportunity to try to figure out who's going to respond, who's going to have toxicity so who should get it? So a lot of accomplishments, but a lot of work still to be done.

Dr. Judy Garber: Well, we all know that research always, whatever questions we answer, it always begets more questions. So, Dennis, you've been thinking really about this in hormone-driven breast cancers for a long time trying to help decide when can we just exploit through hormonally driven breast cancers, their hormone mechanisms. When do we need chemo to help us out.

So, I don't know if you want to talk a little bit about the Breast Cancer Index and we can talk about treatment after.

Dr. Dennis Sgroi: When we're looking at ER-positive breast cancer patients, the estrogen receptor-positive, they have a receptor in their cytoplasm that binds to estrogen, and that estrogen binding to the receptor now turns on a number of genes that actually fuels the growth of tumor cells.

And so, what we've learned from basic science studies many years ago is that if we can, and pharmacologic studies, if we can now block that interaction, we can actually block the growth of estrogen receptor-positive breast cancer.

So, when an oncologist and a patient are together when the patient is first diagnosed, there is really a decision that needs to be made, whether the patient should be treated with chemotherapy plus hormonal therapy. Or if they should be treated with hormonal therapy alone.

And the decision around that is based upon whether it's based on the risk that the patient has for recurrence and that is derived by clinical staging as well as pathologic staging. Which is really what pathologists do. They provide a lot of the information that allows an oncologist to determine that risk.

And also, it's determined on the likelihood of benefit from therapy. And so, we have noticed over the past 10 years and, in particular, what has been extremely helpful in making that decision whether to have chemotherapy or not is the use of Oncotype DX, a molecular test that really tells the patient what their risk is and what is the likelihood of benefit.

And that's at the time of diagnosis. And if the patient now is ER-positive and disease-free at five years, there's another decision that has to be made. And that decision is whether to extend their hormonal therapy beyond five years.

And that's really what the Breast Cancer Research Foundation has funded me to do is to validate a biomarker that we have generated called the Breast Cancer Index.

And this biomarker allows us to now tell a patient what their risk of a late recurrence is. And what the likelihood of benefit from extended hormonal therapy. And this is very important. Just like Elizabeth said earlier that we have to balance the benefit with toxicities. And so that this test will help.

If a patient is at high risk and they have a high likelihood of benefit, then it would behoove one to urge that individual to stay on hormonal therapy. If they're experiencing toxicities associated with their endocrine therapy and if they're at low risk and there's a low benefit then there's a low likelihood that that patient may not need to go on extended hormonal therapy.

So, this test really helps in that unique category. And the impact of that is pretty substantial. I've estimated that about 130,000 women each year in the United States have to make that decision whether to extend their hormonal therapy or not. So we believe that this is very important in helping make that decision.

Dr. Judy Garber: I think we'd all agree that one of the amazing things in breast cancer is that we've learned more and more about the different subtypes. We've tried to really target the therapy so they are specific. But no matter what we do, we know we cause side effects. So, Dr. Irwin, do you think that some of your work can help us to mitigate those side effects while we try to help women take what they need to take to try to fight their tumors?

Dr. Melinda Irwin: Yes absolutely. And that's some of the exciting aspects of my research is that even we're trying to really show that healthy lifestyles, modifiable behaviors can improve prognosis and improve the biology of the tumor, we are also certain that it does improve toxicity and common side effects related to treatment.

So, the women that participate in our trials, while we might not see a favorable change in a hormone or a biomarker for all of them, the majority of them that participate in the intervention definitely feel better, whether it be their quality of life or cognitive function or fatigue, joint pain, other common side effects.

So, I think we know with certainty that there are benefits of lifestyle factors on improving toxicity. What really intrigues me though is the immunotherapy trials. Because as you all know, most of the research has been in lung and melanoma.

And in those studies, a higher body weight or a body mass index has been patients receiving immunotherapy in regards to the efficacy of the therapy.

But those two cancers aren't as strongly related to body weight or body mass index. So, it’ll be intriguing to look into the trials that Elizabeth and others are doing if body weight at diagnosis, body mass index, modifies the efficacy of the immunotherapy. And/or improves toxicity, therefore allowing them to continue with the immunotherapies.

Dr. Judy Garber: Thank you. I mean it is a challenge. I think we have to think about the whole person in completely different ways than we used to. And try to find ways to help with side effects that are not just medication.

So, Beth, you are a surgeon. So you live also at another interface in all of this. And in the same way that we try to give the right treatment. Not too much treatment, not too little treatment, there have been a lot of changes in surgery too. Do you want to talk a little bit about those changes and how you think that they should impact our way of thinking about breast cancer treatment today?

Dr. Elizabeth Mittendorf: Sure. So, I would actually suggest that the surgeons were thinking about right-sizing therapy a long time ago. So as you all, we're probably all of an age to remember when patients with breast cancer would go to the operating room with a palpable mass and if they came out with a mastectomy, they knew the biopsy had shown a cancer. And if they had preserved their breasts, it was benign.

And so, in surgery, we've gone from doing radical mastectomies which was the breast and chest wall muscle to mastectomy to a large number of patients getting breast conservation which includes the lumpectomy and radiation.

And the thing that's really exciting to me in breast cancer is that we're getting closer and closer to being able to tailor even that local, regional therapy based on the tumor biology.

So, the things that we were talking about. As Dennis mentioned, the Oncotype recurrence score. There are a number of trials ongoing to see if genomic assays such as that can be used to identify those patients who will do well with just a lumpectomy versus the lumpectomy and radiation which is the current standard.

And the other thing that I think's really exciting in breast surgery is, again, we've gone from doing full axillary lymph node dissections for women with breast cancer to just sampling with the sentinel lymph node biopsy.

But with some of these improvements in systemic therapy, Herceptin® (trastuzumab), the HER2-targeting agents is what comes to mind, I think it's likely that within the next five to 10 years, we may determine that we don't need to be doing lymph node surgery at all in some of these patients who have tumors that are very responsive to systemic therapy.

So, for me, as a surgeon, the exciting thing that's coming along is an even more important role in the multidisciplinary management of these patients to leverage what medical oncologists and others are doing, benefiting our patients, to right-size that surgical treatment.

Dr. Judy Garber: I'm just grateful, when I started being an oncologist, everybody got chemo. Everybody got surgery. My mother had radical mastectomy. So, I remember those days and what that was like when you woke up with nothing and they sent you home with a sock in your bra. That was what I was told.

Things are differently now. And it's great. What an amazing time to be part of breast cancer research with so much progress, but never enough.

You know what? I think we are, in breast cancer, we are so much of a time. We need the expertise of everybody on this panel and the radiation oncologists who aren't represented today. I don't want to leave them out.

But to figure out what is the best treatment. And of course, the only we can get to the best treatments is clinical trials. Now we're all researchers. We all believe in clinical trials. I think our patients are very brave when they agree to participate.

Dennis, when you think about in your area of this work, either in pathology or in hormone driven breast cancers, what do you think are the most important role for clinical trials? Or what are the most exciting trials that you think are going on today?

Dr. Dennis Sgroi: A number of clinical trials that are exciting to me. The immune checkpoint inhibitors, for instance. All the new targeted therapies. The combination of targeted therapies. And when I think of clinical trials, I think of them in terms of the correlative science. And how can we take information from those trials, study the tumors and come up with biomarkers that are going to predict the benefit from whatever combination of therapies.

And that has been really the focus. It is important to understand can we predict the risk of recurrence. But more importantly, can we predict whether a patient will benefit from a therapy or not. Because we want to be able to balance the toxicities and benefits.

And so, when I think of clinical trials, what I try to do is get involved in trials from the correlative science side in terms of trying to identify new and novel biomarkers.

Dr. Judy Garber: So, it's important that women who participate in these studies agree to have their blood or their tumor or both be used for research as well as for treatment.

Dr. Dennis Sgroi: Yes, yes.

Dr. Judy Garber: And Melinda, you mentioned that your trials also rely on trying to find predictors. And you run, these are trials. You don't just say exercise is good because it seems like a good idea. Can you talk to us a little bit about that?

Dr. Melinda Irwin: Right, yes. They are very tightly controlled trials. Randomized controlled trials where we randomize patients to either receiving the intervention or a usual care control group.

And what's really important is that tightly controlled setting so that you know based on you collect certain data and the outcome variable of interest. And then at the end of the trial, you collect that data again. And any favorable change or any change in that outcome, you know is directly related to that intervention, right?

And so, an important point I want to make here though is that these trials are really critical for proving efficacy. But one thing we've learned from COVID is that we have FDA-approved vaccines. And then when they're in the real-world setting, we have challenges with the vaccine uptake.

And the same thing happens in cancer trials, whether it be a lifestyle intervention or a therapy in that we have to move the trials from efficacy to effectiveness. And then also implementation science trials. Really testing them in the real-world setting. Making sure we have a generalizable sample enrolled in the studies. And better understand how do we get individuals to take the medication or do that lifestyle intervention so that we can significantly improve cancer outcomes.

And Judy had such an important comment at the beginning of this talk where we know eating well and exercising is important. But how do we do that? We all busy. And interestingly, Medicare has covered weight management counseling, about 20 sessions per year for patients who are Medicare eligible.

And yet the uptake of this is two percent. So only two percent of Medical recipients are receiving the weight management counseling. So the implementation science, the testing of these interventions in the clinic, implemented in oncology care, are critical.

And to me, that's the next step over the next decade of research that has to be done. We know what we need to do, but how do we change these behaviors. Or how do we take that medication or that vaccine or what not?

So, it's really exciting because hopefully, this will have a huge public health and population-level impact if we can figure this out.

Dr. Judy Garber: There's always more to be done. Dennis, I want you to talk about what you are most excited about?

Dr. Dennis Sgroi: Well, from the pathology side, there is, I would say the use of digital pathology and computational pathology marriage with artificial intelligence.

And I think that now adding that amount of information to the molecular information that we gain, plus the clinical information. And marrying this with clinical trial outcome data, when we put those together, I think that we will come up with better ways of predicting who is going to benefit from a particular therapy.

So we're still in the infancy as it relates to that. However, I think that that's where it will be most beneficial and most powerful is helping to predict who's going to benefit from therapy. That has always been my mantra. I learned that very early on from Dan Hayes. And I can credit him for that or blame him for that.

Dr. Judy Garber: So artificial intelligence improving pathology. Artificial intelligence improving radiology.

Dr. Dennis Sgroi: Yes.

Dr. Judy Garber: Trying to make us better at finding small tumors or at predicting where on that mammogram something will occur. And I have to say as exciting at this conversation has been, I just want to make sure we realize this has been an amazing few years for progress in breast cancer.

How many new drugs? We have drugs for triple-negative breast cancer. sacituzumab govitecan (Trodelvy®), which was developed at Mass General. And it's already part of the standard of care.

New drugs in estrogen receptor-positive cancer. New drugs in HER2-positive cancer just in the last months two drugs that have moved up in treatment. So research has really changed tremendously what we can do in breast cancer.

But obviously, we still have quite a bit left to do. And I do have one question left to ask and that's just we're still living in COVID. If we weren't we would have been able to be together to talk about this instead of sitting sedentary in front of our computers on Zoom. But I wondered, Beth, has COVID impacted breast cancer care that you see?

Dr. Elizabeth Mittendorf: So, I think it has gone in phases as we've worked through the pandemic. And so, when we were initially faced with what we thought was that first surge here in Massachusetts and a lot of us were told at our institutions we couldn't do elective surgery. We had to be thoughtful about caring for our breast cancer patients.

So at least at Dana-Farber, one of the things we did was to increase the use of neoadjuvant endocrine therapy. So giving patients agents that target the estrogen receptor such as Dennis has described before surgery.

So, I think that's actually been a positive. I think we've learned quite a bit about dealing with estrogen receptor-positive breast cancer and neoadjuvant endocrine therapy.

As we've moved through the pandemic, the thing that I personally feel we're seeing and this might be anecdotal. Although Dr. Connie Lehman at the Mass General Hospital has suggested she's seen this as well. She's the head of breast imaging.

All these women that we've rightly told you don't need to get your mammogram during the height of the pandemic are now just slowly coming back in to get their mammograms. So in my own clinical practice, I'm seeing patients with more advanced disease.

And so, I point that out, in part, to encourage everybody. It's safe to go back. It's safe to get your mammogram so please go get it down. So those are two of the things that I've noticed with respect to clinical care.

And the final thing is I now have patients asking me about the vaccine. And I strongly encourage all my patients to get the vaccine. And when eligible to get the booster.

Dr. Judy Garber: Absolutely, but don't do it right before your mammogram. Because then when your lymph nodes swell up, you'll have to get extra ultrasounds. But definitely do both. Mammogram and vaccine. So well thank you all for so much for spending some time with us this afternoon.

We are so proud of our BCRF investigators. And you guys are just amazing. We just have a great group of incredibly smart people who are all working really hard to make a difference. Thank you for joining us this afternoon and please stay tuned for your virtual tables where you'll have the opportunity to connect with these and other BCRF funded researchers and ask your questions firsthand. And next year I hope we're in person. Thank you.

Outro: That was BCRF’s Boston 2021 Symposium and a special Investigating Breast Cancer podcast. Thanks for listening. To learn more about breast cancer research or to subscribe to our podcast, click here.

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