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Boston-area BCRF investigators joining the Boston Hot Pink Virtual Sympoisum

Watch BCRF’s Annual Boston Symposium Featuring Four Area Investigators

In a wide-ranging conversation, researchers discussed COVID-19, clinical trials, artificial intelligence, and more

Each year, BCRF’s annual Boston Hot Pink Luncheon and Symposium brings committed area supporters together to honor the Foundation’s New England-based investigators—who make up the second-highest concentration of BCRF’s grantees—and raise lifesaving funds for breast cancer research.

In October, the program was held virtually and featured a panel of four esteemed investigators: BCRF Scientific Director Dr. Judy Garber from the Dana-Farber Cancer Institute, Dr. Nancy Lin from the Dana-Farber Cancer Institute, Dr. Constance Lehman from Massachusetts General Hospital, and Dr. Nadine Tung from Beth Israel Deaconess Medical Center.

Watch this timely and informative symposium below or on YouTube. A transcript of the investigators’ conversation follows.


Read the transcript below:                 

Dr. Judy Garber: Hello, and welcome to this symposium for BCRF Boston Luncheon, this is going to be a great opportunity to hear three of Boston's leaders in breast cancer, talk about their areas of specialization, and about bigger issues facing breast cancer research, and breast cancer patients, and breast cancer overall.

You know that BCRF supports breast cancer research across the continuum from the most basic science to applied precision prevention, and everything in between—clinical trials, epidemiology, there isn't an area where BCRF is not active, and that's because we think everything works importantly, together, and all of knowledge is unpredictable and can come from anywhere, and we are everywhere.

We're going to begin by introducing the members of the panel this morning. First from Massachusetts General Hospital, Dr. Constance Lehman, who is the Chief of Breast Imaging. Morning, Connie.

Dr. Constance Lehman: Morning, Judy.

Dr. Judy Garber: Thank you. Next is Dr. Nancy Lin from the Dana Farber Cancer Institute, where Nancy is the Director of the EMBRACE Program for metastatic breast cancer. Hi, Nancy.

Dr. Nancy Lin: Hi, Judy.

Dr. Judy Garber: Last but hardly least, Dr. Nadine Tung from Beth Israel Deaconess Medical Center, where Nadine directs both the Breast Medical Oncology Program and the Cancer Genetics and Prevention Programs. Morning, Nadine.

Dr. Nadine Tung: Morning, Judy. So happy to be here.

Dr. Judy Garber: Great. So welcome, everyone, and let's get started. Connie, do you want to take the first question? Everyone complains about mammograms, everyone worries about breast MRIs and ultrasounds. How are screening techniques and guidelines evolving beyond just annual mammograms?

Dr. Constance Lehman: We’re really excited about the advances in technology, and I do want to say before talking about other technologies, to remind us all that while mammography is just full of problems—the discomfort, anxiety, the missed cancers—it's still the best tool we have, and we've had it for over 60 years, and it's getting better. We're carefully watching over each decade how it's performing. Modern digital, 3D, or tomosynthesis, mammography is still our strongest workhorse, and it's absolutely critical for early detection.

Ultrasound and MRI are two other tools that we use in certain special situations with patients that are at high risk, and especially patients that are at increased risk and for whom we know mammography doesn't perform as well in. But I think the really hot topic in the next two years is going to be contrast enhanced mammography. Contrast enhanced MR, is it's a little bit like driving a Maserati around your parking lot, you're using this MRI equipment just to see where the blood flow is, and we think we can do that with contrast and enhanced mammography. So women that really are challenged by going into an MRI scanner, they won't have to be worried about that aspect of it. It's also a huge, huge way to address the cost of MRI, which is really prohibitive for many, many of our patients.

Dr. Judy Garber: Thank you, Connie, and I appreciate you pointing out that now mammography still has an important role to play and that it has improved so should pay attention. This is not the time to give up mammograms—COVID or no COVID. Thank you.

Nancy, you've had a very special interest in one of the most difficult problems in metastatic breast cancer, and that's been brain metastases. Can you speak to our audience a little bit about where progress has been made in this particularly challenging problem?

Dr. Nancy Lin: Sure. Metastatic breast cancer is breast cancer that has spread from the original location in the breast and the lymph nodes, to other parts of the body, and that can include the liver, the lung, or in fact, the brain. Fortunately, for most patients with early-stage breast cancer, developing brain metastases would be very uncommon. But once patients develop metastatic breast cancer, it can be much more common, especially in certain types of breast cancer, especially HER2-positive or triple-negative breast cancer. Historically, the only thing that we've had to treat patients with brain metastases is radiation treatments to the brain, which although they can be effective, as you can imagine, can have side effects, particularly if we're thinking about giving radiation to the entire brain. And with the support of the BCRF, we actually launched now many years ago, the first clinical trial that tested a targeted treatment against HER2, for patients who have worsening of cancer in their brain and that really set the stage for a series of subsequent clinical trials and most recently, a clinical trial of a medicine called Tucatinib, which is a HER2 oral inhibitor, actually has been shown to not only lead to tumor shrinkage in patients with brain metastases, but also to extend their survival. I think that we have made progress, we still are not able to cure patients who have brain metastases, but I think we have many more treatment options than we did before, and we have treatment options that are much more varied than we had before, so they now not only include surgery and radiation therapy, but also systemic treatments.

Dr. Judy Garber: Well, thank you, Nancy, I think, being the oldest here that the treatment of brain metastasis has changed in the years that I've been taking care of breast cancer patients, and they do better, but certainly not well enough.

Nadine, it's not exactly correct to say that the Breast Cancer Research Foundation only support breast cancer research. We also support ovarian cancer research but we're always glad to hear that progress in breast cancer benefits other cancers too. All of our supporters have families. Can you talk a little bit about how research for one group of breast cancer patients may benefit other breast cancer patients, or patients with other cancers?

Dr. Nadine Tung: Sure. That's a great question. I think of two examples. First, I think a good example of how research initially targeted to one type of breast cancer benefited other breast cancer patients involves a medication known as PARP inhibitors. PARP inhibitors are oral medications, targeted therapies, and there were two large international trials that show that for the women who inherited the BRCA mutations, those with metastatic breast cancer, the PARP inhibitors were more effective, and in fact had fewer side effects than chemotherapy. That became a very great finding. The problem is that only five percent of breast cancer patients have these inherited BRCA mutations. BCRF funded through another consortium, TBCRC, a trial that looked at these PARP inhibitors in other breast cancer patients. What we found in this study was that women who had inherited abnormalities in other genes, that function with BRCA 1 and 2, also benefited from these PARP inhibitors, as did women who had not inherited the BRCA mutations, but whose tumors had acquired the BRCA mutations.

So, here was a trial that initially found, a therapy that had worked in BRCA carriers was now working in women with other types of breast cancer expanding, the population. And of course, I think this may be true for other cancers. We know that women with these inherited mutations develop ovarian cancer, pancreatic cancer, the men develop prostate cancer. There's no reason that the results that we are finding for breast cancer can’t also be applied to individuals with these different gene abnormalities in different cancers.

Dr. Judy Garber: Thank you. I think it's true that we may not have realized all of the ways that breast cancer research can benefit other research, and I think that the lists are even longer than that.

Connie, one of the things that you've been working on this year, so fascinating has been artificial intelligence and BCRF was very excited to fund some of your work through the Precision Prevention Initiative. Can you share with us some of your thoughts about AI and what its future can be for breast cancer?

Dr. Constance Lehman: I think it's one of the most exciting times in my career, seeing the impact that artificial intelligence can have in predicting the future, and the BCRF has been so supportive of this work, and also, it shows that aspect of the BCRF that is really about creative, different ways of addressing and tackling our most challenging problems, and the story really goes back some time with the BCRF. Jack Cuzick is a leader in the field of being able to predict a woman's future risk of breast cancer, and Jack was one of the first ones that said, “why aren't we taking some data from the mammogram, and trying to see if that can help predict a woman's future risk of breast cancer?” He integrated into the Tyrer-Cuzick or the Ibis model breast density and showed that that improved the predictive power of the model. Before that the model had the effects of questions that we've all probably answered when we're checking our own risk. Do we have family history: how many members? Have we had prior breast biopsies? Do we have children at what age? Did we nurse our children? It was exciting to see that the breast density moved it forward, but as a breast imager, I knew gosh, that was just scratching the surface of that rich information. You can look at a mammogram and tell a lot about a woman, especially over time, if she lost weight or gained weight and she had breast biopsies. Were those biopsies, just needle biopsies, or excisional biopsies? Was she treated for breast cancer? Did she have radiation? Not just dense or not dense, but really complex patterns, in fact, so unique that each person’s mammogram is really like her thumbprint. What we wanted to do was use the power of computing with artificial intelligence to extract all of that data and extract information that the human eye or the human brain can't process. We use techniques and AI, and found that the image alone far exceeds our traditional risk factor modeling in predicting a woman's future risk of cancer. We're really just getting started. The area of AI and health is still pretty new. What we really think is if we bring everyone's data together, the data that you see in your clinics, what Nadine sees in hers, the genetic information, the family history, and the imaging, when we bring it all together, I think we really will be able to start to enter into that precision medicine. That has been a bit elusive today.

Dr. Judy Garber: Connie, just to make sure—so artificial intelligence is not robots. It's using computers to help get the maximum information out of digital images, or is there a better definition for your purposes?

Dr. Constance Lehman: It's a great way to think about it, there's so many different domains of AI and some of them feel a little bit scary. Would we feel comfortable getting in a car that a computer was driving, or other areas where AI is being used. This is really using fast, smart computers, to be able to leverage the depth and breadth of the data that we now have technology to collect. But analyzing that data is proven elusive, and this is true in genetics, it's true in my domain in imaging. Computer vision is where you could have a computer very smart to identify subtle differences between note animals, for example, over weapons in the military. We're applying that to skin lesions require two images of the back of the retina, we're applying it to the images that we take in a radiology department in my field. Right now, what we're focused on is mammography and the mammograms. There was a study recently that showed that 70 percent of patients would be very nervous, having a computer alone read their mammogram, and those women can know that we're not there yet. We're not where we could have—someday—because computers are getting smarter and smarter, and better and better in sorting normal from abnormal, but right now what we're doing is we're extracting data to predict future risk of breast cancer.

Dr. Judy Garber: Well, I think if computers can help radiologists to be more accurate, like they're helping pathologists to be more accurate, this can only be a good thing.

Nancy, can you talk a little bit about clinical trials? You run clinical trials. I'm not sure everyone knows the importance of clinical trials and how they can help.

Dr. Nancy Lin: Clinical trials are studies in which either new drugs or existing drugs are tested for a new purpose. For example, they might be tested in a patient who has metastatic breast cancer to see whether a new treatment is better than the existing treatment. The reason that clinical trials are so important is because they really form the basis of essentially all current FDA approvals for new drugs. If we think about anti-cancer treatments, even if we think about anti-nausea treatments, even if we think about supportive care of treatments, such as scalp cooling to help people not lose their hair during chemotherapy—all of these advances are a result of volunteers into clinical trials. As we all eagerly await the data from the COVID vaccine studies [Editor’s note: This video was originally filmed in the fall before COVID-19 vaccines were approved by the FDA at the end of 2020], we can just so much appreciate how important clinical trials are, and I look at the trials and I think my goodness, they've enrolled some of these trials who enrolled 30,000 patients in less than six months. Think about what would happen if it took five years to enroll 30,000 patients—we would be waiting five years for results with vaccine. But that's what happens every day in breast cancer. It's very typical for metastatic breast cancer, phase three trials take two to three years to enroll patients, and we're not talking 30,000 patients, we're talking trials of 600 patients, and then we just have to wait that much longer to know whether a new treatment is going to be effective. Then many, many women and some men around the world have to wait even that much longer before the drug becomes approved and could be, easily accessible across the world. I think it's just, it's hard to underestimate the importance of or understate the importance of clinical trials, they really underpin all of the treatments that we give in patients with metastatic breast cancer. The faster we can recruit to trials, obviously, we want good trials, the faster we can make progress and understand what works and what doesn't and build on what works.

In terms of, you know, why somebody with metastatic breast cancer might consider a trial, of course, there is the altruistic aspect of it, you want to help future generations of women and men with metastatic breast cancer. But there is, some potential to also gain some personal benefit.

Obviously, no one can make any promises of that nature, because some drugs just don't pan out, but just in my own practice, I think of my patients who have been on immunotherapy for more than five years, who started on Tucatinib more than five years ago, or who were on CDK4/6 inhibitors five or six years ago. These are patients who were on these medicines, more than five years before the drugs were approved by the FDA, and they have personally benefited. People go into trials, you have to know what you're going into, you need to understand the risks and the benefits. Some treatments are further along than other treatments. It's a very important discussion to have with your doctor if you're thinking about a trial, because there's not always a trial that's quite right for every patient at every moment in time. It's very important to understand just how important it is to really be committed to trials. We look at the United States, less than five percent of all adult patients of all clinical trials, and that's incredibly limiting to our progress.

Dr. Judy Garber: Thank you. You know, I think in the old days, clinical trials were offered only at the end of the line when there was nothing left to do, but these days, there's so many more promising agents, there are different strategies, even in clinical trials in screening or in prevention.

Dr. Nancy Lin: Exactly. They're not only metastatic breast cancer, but for early-stage breast cancer to try to improve the chance of cure, and as you said, prevention trials, looking at new strategies to try to prevent breast cancer all together.

Dr. Judy Garber: They're also a great place for collaboration, because for us to do these faster, we usually have to work together to get enough patients.

Nadine, apropos of this, what can our BRCA one and two mutation carriers and other inherited patients do to reduce their risks of developing breast cancer?

Dr. Nadine Tung: Well, I'd say that a lot of the strategies to decrease the risk of breast cancer in those who have an inherited risk, many of them are the same that we can recommend for all women to decrease their risk of breast cancer. We all know about preventative surgeries, probably the most effective but extreme, and not for everybody. We know that there are medications that can either lower or block the hormones in our body, estrogen and we know that that can decrease the risk of breast cancer for all women, although not necessarily specifically studied in women with these hereditary gene abnormalities, but medicines have side effects, and while they do lower the risk of the most common type of breast cancer, that hormone fed or the estrogen receptor (ER)-positive breast cancers, they don't yet lower or decrease the risk of the ER-negative or the triple-negative breast cancers.

I would also answer that women always want to know what they can do what in their lifestyle, and we tell all women that if possible, they should get a good amount of exercise, maintain optimal weight, and if they're going to drink alcohol, drink modestly, although these are challenging goals during COVID, but I think they're still worthy goals for all women. I will say that they're knowing the gene defect, for example, in the BRCA1 carriers or BRCA2 carriers, it does lead to specific potential prevention strategies. Just to give you an idea of one or two that might be happening - it's interesting that the other hormone we don't talk about very much progesterone seems to increase the growth through a certain pathway for the parent cell, or the breast cancer cell of origin and BRCA1 carriers. This progenitor cell that leads to the triple-negative breast cancer. Interrupting that pathway, at least in the lab or in animals, seems to decrease the risk of developing breast cancer in the BRCA1 carriers. So fortunately, there is a drug. It's an osteoporosis marketed drugs, Denosumab, but there is now a trial looking at BRCA1 carriers to see if that will decrease the risk of breast cancer. So again, another example of how research in another disease might benefit those with breast cancer and vice versa.

Dr. Judy Garber: Thank you. So, Nadine mentioned COVID. And, of course, because of COVID, we're all here virtually. But COVID has had a huge impact on healthcare, and I thought I'd ask each of you to just speak for a minute about the impact of COVID on the parts of breast cancer care that to which you have the greatest affinity. Connie, what's happening in screening?

Dr. Constance Lehman: Well, COVID-19’s impact on screening has been very dramatic. In March in our state, we were all told to stop screening mammography as it was included in the non-essential services. We really needed to shift efforts and resources to treating COVID patients. The governor asked us to curtail screening mammography and then in late May ask that we prepare to reopen for screening. This happened across the country, and it was so dramatic to see the impact across the country screening plummeted, it quickly went down to 10 percent. and zero percent of patients were being screened compared to the prior years. We have started to recover back to pre-COVID numbers, but we left a lot of women behind. There was a big group of women that we didn't screen across the country. We screened 100,000 women every day, so you can imagine when you're shut down to screening for months, the impact of that. At the same time, we saw other factors that are very concerning. Half of the number of breast cancers that we normally see being diagnosed across the country, or being diagnosed in the spring and early summer, and we're watching that carefully. We're also seeing later-stage breast cancers being diagnosed. I've never seen this before we audit our screening program, we've always had 90 percent of our screen detected cancers are stage 0 and stage I. That is plummeted to 65 percent. Our stage II and stage III cancers being diagnosed and our screening population is significantly increased from nine percent to 35 percent. I've never seen this in my life. We need to really be thoughtful about this, I think we're going to be going into a longer period of time where we have to deal with COVID and deal with breast cancer screening during COVID. I'm really hopeful from all that we've learned about safe practice, that we can have risk-based screening so it won't be off or on, it will be more precise and more selective in who we ensure continues to be screened, and then that group of women we feel that it would be safe for them to wait a year, maybe they would be screened every two years rather than every year. But there are some women that really truly can't afford to delay their screen and we want to make sure that we're set up so that we can accommodate them and that we provide the access. That's the other big challenge across the country. There's a backlog of patients, we have to have our six-foot social distancing, we have different measures to keep all of our patients and our staff safe, which means that we're going to have to expand hours, we need evenings, we need Saturdays, we need to spread out our services. The silver lining is it woke us all up to what we've always dealt with, we've never had the level of access to the full diversity of women at risk for breast cancer that we've wanted, and COVID has really opened our eyes to that. To see the challenges that all of our patients have faced, and we're going to do better. It's something that we're addressing, we're looking at risk-based screening, we're starting to do that, and we're getting prepared and sharing with others, especially others within the BCRF family of what they're doing, what their best practices are, and learning together to keep our patients safe.

Dr. Nadine Tung: I think that that's such an important point, I would really make the point that it's been helpful, especially during COVID, to really know which women can actually do with less treatment, something we don't talk about a lot—less radiation, don't need chemotherapy, and all need less screening, as Connie was talking about. And I think all of that knowledge was the result of trials, clinical trials that Nancy was talking about, and so much of it in one way, shape, or form funded by BCRF. So, I found that so helpful during COVID, to have the results of all of that research to know who could omit some therapies, so that we could balance the risk of asking them to come to the hospital and exposed to COVID versus needing to be treated or to be screened. And that and that's precision treatment and precision screening.

Dr. Judy Garber: Thanks. Nancy, did you want to add anything?

Dr. Nancy Lin: I think that I would just add that there, one of the reasons of many, many reasons to work so hard, and in controlling COVID in our communities, is just the impact it has on breast cancer patients and survivors. And I take care of people who have all stages of breast cancer, but in particular, I feel for people living with metastatic breast cancer who are living year by year, who we hope will have years ahead, but we don't really know how many years that might be. And to have that time, stolen in a way with all the restrictions that are required to keep them safe from COVID infection is really, to me just so heartbreaking. It truly is.

I think in the hospitals, we've done generally a very good job, we've really been extremely careful, we know that our patients are vulnerable, and we do not want to expose them to infection. But it's really our communities. At the same time, breast cancer doesn't stop and that's obviously why we're all here. When COVID is behind us, and I think it will be, I really hope that we have been able to keep this progress going, so that all these projects and initiatives that should just keep going, and or that pay out two to three years from now, we'll still do that. And we'll be there for patients when we get through this current crisis.

Dr. Judy Garber: Well, thank you. It's difficult for people in the middle of the COVID crisis, especially those who still have to come for treatment to the hospitals and the clinics and still have to come for screening. But we certainly are making those places, safe places for our patients to go, so we really wouldn't want anyone to hesitate who needs treatment or needs screening to come and get the care they need. We are making it safe for them to be there, but we also respect that maybe they don't need to be there as much, and things that we can do to reduce the amount of time people are spending in care or in the hospitals, we are certainly trying to do.

Well, thank you very much, all three of you, for a remarkable symposium. I think there are several themes for people who were listening, but really all of you who do such great work, work together, and to work with others to try to have us make progress in the earliest possible stages, that early detection all the way to metastatic disease. Thank you and thank you for sharing your knowledge today. And thank you to those of you who've joined us in this symposium, what a treat you've had. We will all look forward to seeing you in person, hopefully at the next BCRF meeting in Boston.

RELATED: Listen to BCRF's 2020 Virtual Symposium & Awards Luncheon on Our Podcast

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