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Watch BCRF’s Annual Westchester Hot Pink Symposium
Three BCRF-supported researchers discuss the latest advances in breast cancer screening, risk prediction, metastatic treatment, and more
Every year, BCRF’s Westchester Hot Pink event convenes committed area supporters and some of the brightest minds in breast cancer research to support our Foundation’s mission. This year’s virtual program, “An Evening with the Experts,” featured a panel of three esteemed researchers: BCRF Scientific Advisory Board Member Dr. Eric Winer from the Dana-Farber Cancer Institute, Dr. Constance Lehman from Massachusetts General Hospital, and BCRF Scientific Advisory Board Member Dr. Susan Domchek from the University of Pennsylvania’s Perelman School of Medicine.
Watch their informative discussion—touching on everything from artificial intelligence to metastatic breast cancer—below or on our YouTube page.
An edited transcript of the investigators’ conversation follows.
Read the transcript below:
Dr. Eric P. Winer: I'm very happy to be joined by two great colleagues. You've already heard them introduced just a bit, but I'll now take that a step further. So first, we have Dr. Susan Domchek from the University of Pennsylvania. Susan is a professor of medicine at the University of Pennsylvania and focuses largely on BRCA1 and BRCA2 and other hereditary aspects of breast cancer. I will confess that Susan was once my mentee when she was a fellow at Dana-Farber just a few years ago—I won't say how long ago that was. But it's long enough ago that Susan is now a world-famous breast cancer researcher and clinician. Also joining the panel is Dr. Constance Lehman, who is my colleague in Boston, and Connie, is one of the world's most outstanding breast cancer imagers. She has piloted and further investigated many novel imaging technologies. She's been involved in the area of artificial intelligence and breast cancer screening, and her comments will be particularly helpful for those women who are interested in hearing about how best to monitor for breast cancer. So, without further ado, we have about a dozen pre-submitted questions. And I'm just going to start and I'm going to say to all of you that we're going to try to keep this as informal as possible. It's a little funny doing this by Zoom or whatever this particular platform is, but we're going to do our very best, and I'm sorry to say that over the past eight months, all of us have gotten used to communicate in this way. So, Susan I'm going to I'm going to start with you, and you can take this question any way that you want in any direction that you want: Have there been breakthroughs in screening and prevention of hereditary breast cancer? I think Connie may want to comment about some of the screening aspects particularly regarding imaging. But what's new in hereditary breast cancer?
Dr. Susan Domchek: Well, Eric was very kind of you not to date me, but I'll date myself. I graduated from medical school in 1995, which was when BRCA2 was discovered, and since that time we've had an increasing understanding regarding genetics and genetic susceptibility, and also the concept that we've always known, which is that genetic disease isn't everything—but genetics can certainly help us. So we've expanded from knowledge about BRCA1 and BRCA2 into multiple other genes called PALB2, CHEK2, ATM, [and others]. And increasingly, we're also understanding, changes in the genetic code, which have tiny little effects individually, but all together can have a great impact. We call these single nucleotide polymorphisms. We talk about polygenic risk scores, and what all this means. This is why it's going to be so interesting to talk to Dr. Lehman tonight. We want to use this information to risk-stratify patients, so that we can determine who needs screening when. So, people will have BRCA1 and 2 mutations means the maximal screening: they need breast MRI in addition to their mammograms if they're not choosing mastectomy, but there are actually some women in the population, who need less. They actually may need a mammogram every other year, and it's important to differentiate who needs more and who needs less. Genetics is one piece of that, as his breast density and other things that I'm sure we'll talk about tonight.
Dr. Winer: Just to touch on screening issues for women who are particularly high risk because of a genetic predisposition, and [Dr. Lehman], I'm going to ask you to comment about one very specific issue since I'm sure you're going to talk about MRIs. And the question that many women, ask, over and over again is: If I'm having MRIs, do I still need to have those uncomfortable mammograms?
Dr. Constance Lehman: Absolutely and you know there's sort of a foundation of truth that we know, which is that when we detect cancers early, it's much more likely we will cure them and much more likely the impact of the treatment will be lower. And we have decades and decades of research in mammography, and mammography itself has gotten so much better, that when I pull even old comparison mammograms from 1990, I have to remind myself we used to think that those were really high-quality exams. We can go back to the late 1960s, when we were first screening, and we can't imagine they were able to find anything. And for all the problems and all of the challenges of mammography—the missed cancers, the discomfort, the concerns about radiation—it's still the best tool we have for early breast cancer detection. It is. It's the standard against which we keep trying to get better things. And so, we want to remind women. You know it has its problems, but it really is the best test we have, and we still strongly encourage women to get their routine mammography.
The question and the domain of MRI is really important. I'll cut to the chase a little bit on what I'm most excited about in the domain of MRI. I spent most of my career studying MRI—the clinical utility of it. We were surprised [to find] that in some patient populations where we thought it would be a great tool, it [didn’t work well], and other areas where we thought it'd be sort of a lousy tool, like screening, it actually worked really well. But we also found out over time that very few women had access to the quality MRI programs that we thought would bring such benefit, and that there were problems with MRI as well with false positives women. Sometimes someone just didn't operate the MRI well, and really what the MRI was doing was showing us areas where there was abnormal or different or increased blood flow at very specific spots, and it's that increased vascularity that we were looking for with the MRI, so we're pretty excited about some new methods of … imaging that shows us these increased vascular spots, such as contrast-enhanced mammography. I think that's going to be a very important development in the next few years. How can we provide greater access to contrast-enhanced mammography? My gut instinct is the reason why a long time ago we thought contrast-enhanced MRI wouldn't be a great screening tool is because of the expense, and the challenges in having global access or access in a diversity of communities across the country to really high-quality breast MRI. I think contrast-enhanced mammography might cure that. But you also ask, do you still need to get a mammogram? I actually think you do. I've got some really bright colleagues, especially in Europe who think that you might not need to get the MRI itself, and would be sufficient. But we still see certain types of cancers, especially the early ones that we still like to know about—the ductal carcinoma in situ (DCIS). We see many of those cases are better on the mammogram. So … if you talk to experts around the world, the jury's still out, and especially in US Centers. But we really want women to continue their mammogram along with the MRI if they're at high risk.
Dr. Domchek: And we tend to stagger them so that every six months a woman is getting either an MRI or a mammogram, and that makes me feel better. We certainly have detected things on those intervals. The mammograms, you know, in the end, again we're talking about women at the highest risk. Not everybody needs an MRI. I'm sure that we're going to talk about that more.
Dr. Lehman: And I also like, Susan, what you were saying about how we're really trying to move to precision medicine. We're trying to be more precise and as we're looking at all of these different factors that that you're developing with your team and that you're testing and studying it's, you know what, which women really need more intense screening, and which can do really well with less intense screening. And what we're excited about and what I love about the BCRF—they’re always approaching this from a multidisciplinary perspective—is that we're looking not only who's going to have cancer but which of these screening modalities, best suits these different women. We’re pretty basic in that right now. Someone with very dense breasts we’re saying, ‘Well, the mammogram may not be as good as an ultrasound or MRI.’ Where someone might have more fatty breasts then it's like, ‘Oh, the ultrasound might not help.’ But that's just scratching the surface of where we can really get to, particularly with some of the new tools that we have in our toolkit for being more precise about screening strategies.
Dr. Winer: And before we leave that. We heard from [BCRF Board Member] Nina Garcia who acknowledged that she had a genetic predisposition to breast cancer and that she ultimately decided to have bilateral prophylactic mastectomy, which of course does dramatically reduce the risk of developing breast cancer, but you think that there will be a future time when our screening and treatment is so good that our woman—and she is one of many, by no means was she unusual in that decision—but, will there be a time when a woman doesn't need to make that decision because she can be rest assured that if she develops a cancer, it will be crafted early and treated so effectively? I guess I pose that to both of you.
Dr. Domchek: I'll jump in first—I’ll let Connie take that early detection question—but let's not forget about prevention, and we definitely want to think about non-surgical prevention. They are really interesting studies that are ongoing or about to start in the U.S., and those include such things like a bone strengthener medication called donafenib, which preclinical data suggests it may decrease the risk of BRCA1-associated cancer. We actually have FDA approval to start a vaccine trial in BRCA1 and 2 mutation carriers. So, we don't know which of these things will work. But we have to keep trying non-surgical prevention techniques, because if we can get our risk down by 50, 60, 70 percent, then we have really good screening—then that seems like a really reasonable option. So, we need to work on things simultaneously.
Dr. Winer: And Connie, do you think we're going to see further advances in screening for women who are at very high risk.
Dr. Lehman: Absolutely. We're really excited about this domain and, you know, I agree. It's so interesting when we think back. I remember as a medical student, an epidemiologist was talking to us about cervical cancer, and what the patterns that she had been studying and seeing and she just mused like, you know, would it be possible that there could ever be a vaccine, because some of these patterns, it looks like there's an infectious component because of the populations that were more likely to get cervical cancer and less likely to get cervical cancer and [now] here we are with the vaccines that just have dramatically reduced that cancer. Breast cancers seem certainly to be more diverse types, and there may be many different types of disease, but a vaccine against many forms would be so exciting. … I think we'll probably talk about it sometime this evening, but we're so excited in the imaging sciences, not only for how we can be more precise in screening, but finally been able to extract predictive data out of every woman's mammogram, out of her ultrasound, out of her MRI. It really helps piece together: Are these interventions to prevent or reduce risk? Are they working? Do we already see changes in these signals over time? That marriage of genetics and imaging proteomics and genomics—it's an exciting time of big data.
Dr. Domchek: We've always struggled in the prevention field in that we do have a medication that decreases risk in the general population by 50 percent: the drugs Tamoxifen, aromatase inhibitors. But people don't want to take them, and I understand it if there's side effects. What we don't have is a marker showing people that it's working. And I try to remind patients that you take cholesterol-lowering medications to prevent a heart attack and a stroke. You actually don't really take cholesterol-lowering medications just to lower your cholesterol. But in breast cancer, we don't have that intermediate biomarker, and we're hoping that some of our colleagues come up with it. Because if we can show people, you're taking this, and we can see that it's changing your breast tissue and reducing the risk, I think we'd have much higher uptake of our medications.
Dr. Winer: The next question relates to what's sometimes called the de-escalation of therapy. And it's specifically as what is the de-escalation of therapy and how can this benefit patients, and I'm going to start with this, but I'm actually going to then turn to each of you about this one is, as well. So, breast cancer research at the moment is sort of a tale of two paths, and one path is about trying to figure out why it is that some women develop recurrences of breast cancer, recurrences elsewhere in the body that has metastatic breast cancer. And ultimately, sometimes after many years, they die from breast cancer, which is absolutely what we want to try to prevent. And, of course, there are some women who even at the time of their initial presentation already have metastatic breast cancer, we're going to be talking more metastatic breast cancer later. And for those patients, much of what we have to study, is how to avoid drug resistance and how to come up with better therapies.
But there's another very large group of patients who, at the moment, are absolutely cured with the therapies we have. And one of the big questions we have is, whether we can actually do less and still achieve that same very favorable result. Because the truth is that all of our treatments have some side effects: getting chemotherapy certainly has side effects, taking five or 10 years of hormonal therapy has side effects, surgery is not necessarily pleasant, and radiation has side effects, just to name a few. And so, what de-escalation is about—and I actually don't really like the term de-escalation, although I may have been one of the people who coined it, I like to call it right-sizing therapy. And what that's about is trying to come up with the right therapy for the right person, and in medical oncology, we certainly think that we've invented this idea, of course. The surgeons and radiation oncologists have been asking these questions for several decades. But in medical oncology, what that has been about is largely trying to get rid of toxic chemotherapy. And we've done that successfully in many patients with estrogen receptor-positive breast cancer. We learned that many of those women who are diagnosed with estrogen receptor-positive breast cancer have either little, or in some cases, no benefit from chemotherapy. And we've also been able to do it in another setting in so-called HER2-positive breast cancer, where, in fact, we have medicines that are alternatives to chemotherapy. And these are drugs that are directed against the HER2 receptor. And there we can often use much less chemotherapy, in combination with what are often antibody therapies, and that's particularly true for women who have early stage HER2-positive breast cancer.
But I think the take home message is that we are very aware of the side effects that we induce and the long-term toxicities that come from some of our therapies. And while, in exchange for preventing a recurrence of cancer and preventing a woman from ultimately succumbing to metastatic breast cancer, those side effects may be well worth it. But if we can achieve the same result and ensure that a woman is going to do well, then it certainly makes sense to dial back on those side effects. I'm going to ask, Susan to just expand on that a little bit. And then, I'm actually going to ask her, and I'll say right now. I'm going to ask you, so you can just go ahead. I'm interested in in Connie's thoughts about backing off on the frequency of mammography for some women, which is something that that Susan referred to earlier.
Dr. Domchek: Right, and this all relates to each other. When I was training under Eric as a fellow, you know, every woman who had a one-centimeter tumor that was estrogen receptor-positive and lymph node negative, which is a low-risk situation, we talked to every one of these women about chemotherapy. In that situation, which is pretty incredible to think about now, because on the basis of large, randomized trials, we now know that 75 percent of those women don't need chemotherapy, and we know it based on these genomic assays. The most common one in the United States is called an Oncotype DX assay. … Now, [a postmenopausal woman with a] node-negative, estrogen receptor-positive tumor doesn’t get chemotherapy. And this relates to imaging, because one of the downsides of imaging that has been proposed is that we find cancers that a woman might have died with and not of, and now we’re overtreating all these women. But now that we're giving so much less chemotherapy, we have to kind of rethink about that a little bit, because we're not giving chemotherapy to everyone. And so that's a really striking thing—the amount of chemotherapy we give now is so much less than what we gave for and yet, overall, women have better outcomes. I mean, that's pretty cool.
Dr. Lehman: Yeah, I really liked the way that you framed that, and I couldn't agree more. We keep looking whether it's de-escalation or whatever the term is, it's trying to be more precise. It's trying to say: One size doesn't fit all. We have multiple different shoe sizes because of all the different kinds of feet around, and we're trying to do that across all the disciplines in surgery, genetics, imaging. It's always interesting for me to think back historically. It's a very sensitive topic among breast imagers about when to start, how often to screen, and when to stop [screening]. If you want to get someone excited at a dinner table with a bunch of breast imagers just open that topic up for conversation.
If I go back to some really interesting advertisements from the American Cancer Society in the 1970s. It has a picture of this woman and she looks like she has had a lobotomy—she just looks like she cannot make any rational decision. The ad says, “If you're over 35 and you haven't had a mammogram, you need more than just your breasts examined—you need your head examined.” This was over 35 in the 1970s Now, we come forward a little bit and the American Cancer Society comes back and says, ‘Well, we meant that you needed your head examined if you were over 40 and haven't had a mammogram,’ and then they came back and said, ‘Actually, what we really meant based on the science was 45.’ So you can imagine that with these changes, organizations review new data and try to adjust. It's been an area that has been so frustrating for so many women that just want to know, ‘When should I start? How often should I have this test? And when should I stop?’ So, we need to be more precise about it.
Those of us that really work in the domain of breast cancer are so focused on early detection. Sometimes it's confusing to think, Well, why wouldn't you just screen everybody every year for 30 to 40 years starting at 35, and it's because of what Susan has said. There are harms associated with that. There are a lot of women who we may not know them as much, they've never had breast cancer, but they've had multiple biopsies surgeries, they sort of had a big chunk of their life where they actually didn't feel particularly healthy they might have stopped exercising because of their breast disease and so my friends that are in primary care and they see these women more, and they are concerned about the impact of “over screening.” Over, under—it's just not precise. I feel very confident that we are right at the brink of getting into more precise screening strategies for women, and I'm really excited about it. We've gone through a few decades of exciting advances in the technology of imaging, and now this next phase is taking all of this data that we get from a modern digital tomosynthesis mammogram or from a high-quality ultrasound or from an MRI or contrast-enhanced mammogram, taking that and having a strategy that we can really safely say this woman really would do well with this particular, fairly low intensity screening strategy, where this other woman needs a more intensive screening strategy.
Dr. Winer: Thanks. And I guess we now all know how breast imagers or radiologists in general have a good time. You know I guess we all have our ways of building up a dinner tables conversation. So, Susan, can you just comment on how research for one group of breast cancer patients let's imagine either patient with BRCA mutations or patients with ER-positive breast cancer, you know, any group can benefit others with breast cancer.
Dr. Domchek: Absolutely. … I'll give you, as a precise example, which isn't directly in breast cancer but it's helpful. When we are looking at BRCA1 and 2 mutation-related cancers, drugs were developed to specifically target the cancers with those gene mutations. They're called PARP inhibitors, and they were developed with BRCA1 and 2 patients in mind for very good reasons because of the specific DNA damage deficit that was in the cells. And so, we develop these PARP inhibitors, they get approved initially in BRCA1 that's related to cancer. But now it's very clear that, particularly in ovarian cancer, there are a large number of cancers that don't have BRCA1 and 2 mutations, but they do respond to these drugs. We're still trying to sort that out in breast cancer and we haven't exactly identified which breast cancers that don't have these gene mutations will respond. But you have to dig deep on the science so once you get a hit that you will want to have a positive result. You then have to say to yourself, ‘OK, how else does this work? What can we do with them next?’
Another very good example is Herceptin and all these drugs against HER2-positive breast cancers. They're used now in other HER2-positive cancers of different cancer types. So, we really as oncologists, you know, sometimes yes I'm a breast cancer oncologist, but I really do try to pay attention to advances in other diseases, because I'm never sure when it's going to cross over. And we have to be open-minded enough to say, you know what that might be relevant. We might be able to use that information. This is basic science. We can't say enough about that. The three of us are more clinically oriented, but we have our basic science colleagues, and sometimes you would never be able to guess what their work is going to lead. … I know science and I sit there, and I say, how will this move from A to B, and yet circuitously it does. And so, we have to be there on the other side listening to [basic scientists] and direct them into the right area, so that they can use their advances to help people.
Dr. Winer: Great. I promised we would come back to this whole area of artificial intelligence. Another approach that certainly was initially considered outside of breast cancer imaging. And I'm interested, Connie and I think everyone listening will be interested, is what you're doing with artificial intelligence and with some of your collaborators at MIT, to ask new questions about the normal mammogram, or MRIs or whatever.
Dr. Lehman: I really like how Susan talks about the importance of listening and paying attention to experts in different domains because that's really where we are in healthcare with our friends and colleagues in artificial intelligence. Having people, such as Regina Barzilay, who's part of the research that we're doing in AI and breast cancer funded by the Breast Cancer Research Foundation, having this woman who was an expert at the top of her field—computer science and artificial intelligence—go through her own breast cancer treatment and just say, ‘Can't we take what we're doing in artificial intelligence and apply it to help women who are at risk for and who are diagnosed with breast cancer?’ That just started to open all of our eyes up to the possibilities. A really strong [BCRF grantee] Jack Cuzick, some time ago he said, ‘Why don't we take the breast density and the mammogram and add it into our risk models,’ and others had been noticing this as well. And so, adding breast density to risk models makes those models better predictive. But what an amazing thing when you think about the richness of the deep, deep digital data in every woman's individual mammogram. And all we're doing is pulling out things like dense or not dense, it's just it almost is going back to when we didn't have any imaging at all, and a woman whose evaluation for breast cancer was just how did it feel in the breast with having no X-ray, no mammogram, no ultrasound of it, we would just practice with that. So that's what has gotten us really excited. We're realizing that with the tools of artificial intelligence, we can actually move from the revolution in improved technology, bringing more data forward to now this revolution of having artificial intelligence tools to extract that data to predict the future. We are amazed at how quickly this work can evolve. … So it's a huge field. It's a big domain right now, and we're most focused on the huge value of the quality and quantity of digital mammograms that we have unknown outcomes of patients. And, and we're just delighted with how many people are excited and interested because it's more information that we can merge with other big datasets, to really be more precise and not leave all this information inside the mammogram but extract it out and pull it forward.
Dr. Winer: I think we've all been fascinated by the work that you and Regina have been doing together and it's great. So the next question is actually one that I will start off to answer, and it's what advice would you give to a patient with metastatic breast cancer and their families. And I was just trying to figure this out. So, I'm 63. And my guess is that I have spent at least five years of my life, in terms of total number of minutes, taking care of patients with metastatic breast cancer and maybe more than that. It's certainly been a large part of the time that I have spent professionally over the course of these many years. So metastatic breast cancer, as everyone knows, is breast cancer that has spread outside of the breast and to distant sites—to the bones, to the lungs, to the liver, to the brain. And typically, we think of this as an incurable condition. That said, it is a very treatable condition for many, many women, and for years.
We were always afraid to acknowledge that we thought that our treatment made people live longer. We thought that if we compared no treatment versus treatment that almost certainly what we would give different people would make them live longer and live better, but we didn't truly have proof of it. And now we do unequivocally, and in the past five years, there have been multiple large clinical trials, each of which has demonstrated that by changing a drug or adding a drug, we are able to improve survival. And in some cases, by a substantial amount for women with metastatic breast cancer. It doesn't change the fact though that at least at this point in time for the vast majority of women, even though the cancer can be controlled and sometimes controlled for five and 10 and 15 years and in some rare cases well beyond that, it ultimately threatens someone's life, and this is what we desperately want to do research to avoid.
And so there is a tremendous effort going on in drug development and understanding resistance to therapies to try to really do better by people, and I'll share with you the fact that there's even thought that for women who, when they're newly diagnosed, and have metastatic breast cancer, so they've never received any treatment before that, there may be even a subgroup of those patients, where we perhaps should think about things differently and should take more of a curative approach in those individuals. There are clinical trials that are going to go on that will address that.
I have to say that as a clinician taking care of patients with metastatic breast cancer is both one of the most rewarding things that I do in my life, and also one of the most challenging because of course, as a clinician you get very close to people and their families, and you see that at times, they don't do as well as you would like. But I do think it's very, very important for people to remain active and hopeful and optimistic because the truth is, you just don't know what's going to be around the next corner and given the pace of research. If someone who's newly diagnosed, for example, with metastatic breast cancer, can, can live for several years, we don't know that there isn't going to be a better treatment in several years that’s then going to be the curative approach. So, I stopped talking in just a second, but I would tell a newly diagnosed patient, that in fact, this is a challenge, and that there's good reason why it's very disheartening but at the same time, one has to go ahead and live one's life and be very hopeful about the future. Susan?
Dr. Domchek: Just as a historical perspective, HER2-positive breast cancer used to be our worst cancer. And now we have so many options for HER2-positive breast cancer in the metastatic setting, which is completely different than again, when I was doing my training. But, you know, the other thing is that it's like Eric said: Try to get educated and enroll in clinical trials when you can, because clinical trials and research are the path forward. Find a team that you have a good relationship with. Your oncologist is going to be your oncologist for the long term. And so, you better like them, and if you don't find somebody else.
Dr. Winer: There we go. I often tell people that when you're healthy, the amount of your “quality of life pie” if you think of quality of life as a pie that can be divided up into little pieces, it doesn't really matter who your doctor is all that much. But when you have a significant medical problem, that relationship with the healthcare team is critical. So, we have two minutes left, and we're gonna do a so-called lightning round question. And this is: Why should people participate in clinical trials? What's in it for them and what's in it for other people? Just quick thoughts about this and then we'll wrap up. Connie there are clinical trials in imaging for sure. Why should somebody do that, as opposed to just get standard imaging?
Dr. Lehman: This is how we learn. We get better. So many of our trials actually are helping women now. I think back on the clinical trials and MRI where those cancers would not have been found, except with the advanced imaging we were doing in those clinical trials. Especially when our clinical trials engage the full diversity of women at risk for this disease, and I'm also we're doing a lightning round. I have to give a shout-out to say to all of you that are watching tonight, let's please remember also to come in for screening right now. Hospitals and breast imaging centers all over the country have mitigated the risk of COVID. We are very concerned we're finding in our center that we are finding cancers at later stages. We are screening fewer women, and we are finding overall fewer cancers at our whole institution and across the country. In the spring of 2020, the cancers diagnoses were half of what they were in the spring of 2019, but the cancers are still there. We need to have safe ways to screen women, and we're so grateful we're using some of our AI technology to bring the right women in while we have such limited access. So I just want to say research trials are so critical—and then also please, please continue to be screened while we can.
Dr. Winer: Susan, from a medical oncologist’s standpoint, why should people participate in trials? You and I both enroll dozens of patients in trials every year.
Dr. Domchek: Just as a reminder, we never open a clinical trial unless we think that it might be better than the standard of care. We don't know if it's better than the standard of care. We talk about being in a position of equipoise. We're not sure that's why we have to do the trial, but I can assure you that we never open a trial, if we think that the other arm is worse. So, we're always trying to get better. We don't know that it will help you. We don't know that, but we hope that it will help future women who are going through this. We want it to help you, but we also know that the answer to the trial will give information that will be helpful to others. So, thank you all for, who those of you have been in clinical trials. We are immensely grateful and always a little humbled. When people come on these studies, so thank you.
Dr. Winer: And it’s true, as you alluded to, it does help many people. And the reason we know more about breast cancer than we do about almost any other malignancy is because women and occasionally men with breast cancer can step forward to participate in trials.
So, our time is up. We really appreciate everyone listening. Just a comment about COVID, it's going to end someday. Unfortunately, breast cancer isn't waiting for COVID. So, there is still cases of breast cancer. We still need to take care of patients, and there even some data that there may be more cases of advanced breast cancer diagnosed today than perhaps a year ago. Maybe that's related to the fact that there's been far less screening. But it just means that the work that we do is going to be that much more important in the future, and we need to we need to continue this momentum for quite some time to come. I want to thank the audience for all your support. Without your support BCRF couldn't do what it does. And we wouldn't make the kinds of strides that we have made and that we anticipate making in the future. We hope that this has been helpful. I got a chance to see my friends Susan and Connie. And I hope you enjoyed it as much as I did. Thank you so much.