Every winter, BCRF supporters in Palm Beach—our late founder Evelyn H. Lauder’s longtime home—come together to support the Foundation and hear about the latest advances in breast cancer research.
This year’s virtual event featured a symposium with four BCRF researchers: BCRF Scientific Advisor Dr. Judy Garber of Dana-Farber Cancer Institute, Dr. Constance (Connie) Lehman from Massachusetts General Hospital, Dr. Graham Colditz of Washington University School of Medicine, and Dr. Lisa Carey of UNC Lineberger Comprehensive Cancer Center.
Watch their informative discussion below or on our YouTube page.
An edited transcript of the investigators’ conversation follows.
Dr. Garber: At BCRF, we encourage researchers from different scientific disciplines to collaborate, to think outside the box together, to explore new theories and follow promising leads that bring us closer to our ultimate goal, the cures for breast cancer and its entire prevention. So, for today’s panel of BCRF-funded investigators, we have a multidisciplinary group tackling research, and I am sure they will have exciting insights to share with all of us. And first, I’d like to introduce Dr. Connie Lehman, who is the chief of Breast Radiology at Massachusetts General Hospital in Boston, and a professor of radiology at Harvard Medical School.
Dr. Lehman: Thanks so much, Judy, I’m really delighted to be here, especially during these really unusual times. It’s exciting for us to be able to share our work, discuss with our colleagues what we’re most excited about, and just be back part of the family for BCRF. So, excited about today. My particular research in AI, in imaging is really at a point where we feel we’re just getting started, so I’m excited to share more about that today.
Dr. Garber: Well, and BCRF is excited to be part of that beginning. Dr. Graham Colditz is the Niess-Gain Professor of Surgery at the Siteman Cancer Center at Washington University in St. Louis and an epidemiologist. Dr. Colditz?
Dr. Colditz: Thanks, Judy. It’s great to be here today. Again to share some of the work that BCRF has made possible. My focus is now for 31 years trying to understand how lifestyle really can be driving the pre-malignant lesions and changing risk of breast cancer later in life. So looking particularly at childhood and adolescent behaviors, and we’ll talk about that in a bit.
Dr. Garber: Great. And last, but certainly not least, is Dr. Lisa Carey, who is the Richard and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research and the deputy director for Clinical Sciences at the Lineberger Cancer Center at the University of North Carolina. And [she] has many other titles, but that would take too long, Lisa.
Dr. Carey: Hi, thank you. So I’m a breast medical oncologist like Judy, but my area of interest, and I have to thank you BCRF for longitudinal support of that is really developing clinical trials, testing novel drugs and approaches, and building in interactions with scientists so that as we’re trying to understand what’s working, we’re also trying to understand why, and so in those roles I actually do things both at North Carolina but also through a consortium of academic centers called the TBCRC that BCRF has funded and has supported for years since its inception and also with the National Cancer Institute-supported Cooperative Group. And I know that BCRF actually was part of my very first trial that I did as a junior investigator that helped me build in the scientific correlate. So I’m hugely indebted and so happy to be here, thank you.
Dr. Garber: So let’s get started, and Connie, why don’t we let you lead off? Can you talk a little bit about what are the most effective screening tools today and what the guidelines really are trying to do about screening? Always an important topic for people trying to stay healthy.
Dr. Lehman: So we know screening saves lives. We know when we detect early, we can cure, but we also know that the workforce that we have in screening mammography has its limitations. Without question, it’s the strongest tool we have. So we really encourage women to make sure that they, their friends, their family members are routinely screened with mammography. One of the areas I’m really excited about is how we as a group can move from age-based screening to risk-based screening. Still when you see the discussions and arguments about, “Should you start at 40 or 50, be screened every year, every two years, should you stop at 74 or 85 or never?” It’s really all about age with a very high-risk group that set aside and said, “Well maybe you also need MRI.” That’s been the case for decades and that’s just not where we want to be. So we’re really excited about being more thoughtful about having more precise recommendations, more tailored recommendations for screening for our individual patients. And I think that’s the domain of screening that’s most exciting. Certainly as a radiologist, I also think about the tools to screen with: mammography, tomosynthesis mammography, ultrasound, MRI contrast-enhanced mammography. Which of these tools should we use in these tailored approaches to our patients? But I think first we need to do the hard work of embracing risk-based rather than age-based screening.
Dr. Garber? Thank you, Connie. And now you’ll see that this all links to Dr. Colditz who has spent his career trying to figure out how do we predict: What’s risk? What are the risk factors? And how do we identify women who have highest risks so we can at least now think more about how to use that information to target and tailor their screening? So Graham, for you, we thought we’d begin by asking about risk factors, of course, and their role in identifying opportunities for prevention. How can we use them to help think about reducing that risk?
Dr. Colditz: The challenge clearly is to integrate risk across life and across different lifestyles. We know that obesity or adult weight gain say from age 20 on is probably the largest driver for menopausal breast cancer. And so avoiding adult weight gain, even losing weight and keeping it off, is related to lower risk in post-menopausal women. But we need to put that in a context of diet and physical activity, alcohol and integrate these so we can actually get to a summary measure of the lifestyle factors and bring in features from mammography, bring in genetic scores and really get to the stratified risk screening that Connie’s talking about. The interesting challenge here is that the childhood adolescent pieces have not been anywhere near as well-studied as midlife and older women and risk factors in shorter term. And yet there’s growing evidence and BCRF has funded my work to really look at how childhood adiposity, diet, nuts and so on in the diet, fruits and vegetables in childhood, adolescence, actually impact risk long-term. And so you can pull these together into a summary that’s accumulating risk over life to better stratify the modifiable risk factors and feed that into the AI algorithm that will give us the best technology for the level of risk, rather than really just using age as a marker.
Dr. Garber: Lisa, we know what we know in risk, what we know in screening, and certainly what we know in treatment from clinical trials. Can you talk a little bit about why clinical trials are so important and particularly why metastatic breast cancer patients might think about participating in clinical trials today?
Dr. Carey: The short answer is we’re not as smart as we think we are. So you have to do trials in order to test hypotheses. I mean, I may think I have the best possible answer to something based on preclinical information from laboratory scientists or things like that. But unless you actually test it you don’t know what truth is. And I think of clinical research in metastatic breast cancer in two ways: One is drugs and testing new drugs and if they work in metastatic cancer then you can try moving it into the earliest setting where more is the goal, and the other is biomarker studies. We have quite a few studies where patients are actually allowing us to obtain biopsies to understand how the cancer changed from when it started to when it became metastatic, because there are differences in what is it about those cancers, so what two of them that look the same to us at the outset one relapses and the other doesn’t, how do we understand that better? And you can only do that through trials.
Dr. Garber: So, Connie, I think everybody said, we wish we were smarter, we need to know more, and you have been trying to use a totally new way of looking at this with artificial intelligence which maybe will make all of our intelligence look better at least, trying to find a way to improve the technologies we have. Could you talk a little bit about that for us?
Dr. Lehman: Absolutely you know this domain, this frontier with artificial intelligence, is probably going to in hindsight be one of the most impactful in health care that we’ll experience in our lifetime. Because AI, isn’t just one thing, it’s not, oh we’re using AI at our center for this specific application. AI is a tool, it’s basically leveraging the fact that we have much smarter, much faster computers that allow us to perform tasks that we just couldn’t do before we had these fast computers. So AI is a tool that we can apply to every single problem that we have. Every question that we have. How we apply it, how we leverage the strength of the tools of AI, and how we as humans integrate the tools of AI into our practice to improve the lives of our patients. That’s also on us as well. What I’m so excited about and every time I have an interaction with the BCRF community, I get more excited. Listening to Graham, as he was talking about the importance of weight and obesity and fat. What we think that we’ve discovered with our AI tools is that our models can detect through computer vision, subtle cues on the mammogram, that our human eye and our human brain can’t identify. Now what we know as mammographers, as breast imagers, is I can look at a mammogram and say, look, this woman really was overweight before, and look how we see these signs that she’s lost weight on the mammogram. However, my eye and my human brain is pretty limited in quantifying that, but the AI tools can see that because we can train them over hundreds of thousands of mammograms to detect those cues. Weight is just one. What about the risk of cardiovascular disease through those calcifications on a mammogram? And then what about all the cues that I actually am not even aware of that none of us are? Because at the end of the day, most women diagnosed with breast cancer have no known risk factors. That tells us something. So when we have an AI tool that is outperforming traditional risk models, and we start to ask what does is it seeing? I’m almost glad that at first blush, we’re not sure what it’s seeing, because those are the women we’re trying to find. Those women that the AI is telling us pay attention to this woman when every other traditional risk factor seems to be okay.
Dr. Garber: You know we can all feel your excitement and it’s great to have a piece of your work that you really feel is going to make a difference. So we’re glad to be part of that with you. Graham, you talked about obesity and it is always a challenge for post-menopausal women, maybe more so than everyone else. There are other risk factors that we have some control over. And if you think that this is more about adolescent exposures and childhood exposures, how can we be thinking about keeping our family safe and ourselves safe? What else haven’t we talked about yet that you think about?
Dr. Colditz: That’s a really good question, Judy, because clearly, we model, and we serve family meals, and we do set, in a way, the habits of our children, our grandchildren. And from the diet-activity side, there’s the walking and all the things we can be doing. But the diet piece of shifting to a more plant-based fruits and vegetables, really starting in childhood and maintaining through adolescence, is sending a pretty consistent signal at this time that the higher intake is related to lower risk of proliferative pre-malignant lesions in premenopausal women and signaling multiple studies that these higher vegetable diets, actually lower risk of receptor-negative breast cancer. So it’s, across the life course, yes, but we are influencing our children and grandchildren. Other pieces, particularly for post-menopausal women, menopausal hormone therapy are major contributors, so shortened duration or none at all is clearly a reducing risk. And we know what alcohol in adolescents and before first pregnancy, higher intake across those years from adolescence to first baby, lifetime increased risk of breast cancer. And in the subsequent years, alcohol intake is still contributing to risks. So for all of these, whether it’s exercise (do more), alcohol (do less), yeah, zero may be best but we can all make an effort to cut back and when you put those together you really can start to change risk at the population level.
Dr. Garber: So COVID really is a problem in many ways because alcohol intake has gone up at least 50 percent according to the statistics, which we can all understand. And I hope it’s not the COVID 19 like the freshmen 15, whatever it was. Lisa, in your role at the Lineberger, I think you’ve probably seen the impact of COVID, a little bit on care, on people’s concern about the safety of coming for mammograms but also coming for treatment and worrying about their care. It’s led some people to do more virtually by the Zoom that has become ubiquitous in our lives. Can you talk just a little bit about this?
Dr. Carey: I keep hoping that now that there are vaccines this is all going to be over, but I don’t think it’s going to be over so quickly. We have certainly started bringing patients back in for regular care. We never really stopped our infusion center dropped 5% in the very beginning. Because the patients who need care, need care it doesn’t matter if there’s a pandemic going on or not. I hope we don’t go back to completely the same. So you mentioned telemedicine. So telemedicine is something we’ve all thought would be better for our patients for years. We just didn’t have a tool to do it. It’s clear you can deliver effective care. You can identify patients appropriate for telemedicine or not. And it’s better for their care in general, regardless of the pandemic. So I hope, I think we will get back. I think we already have gotten back to regularly, fairly regular care for patients in the outpatient setting particularly. But I hope we don’t lose some of the advances that I think are really good for our patients and may have been spurred by the pandemic and changes to the pandemic but actually should live on beyond that.
Dr. Lehman: In many ways, COVID sort of opened our eyes to what we always knew was there, but it really unveiled a lot of the inequities that we were seeing. So in Boston, at Mass General we saw a shift when we came back to resume screening, after screening by our state was shut down as it was across the country. And what we saw when we reopened was a difference. We shifted to screening more white women and fewer women of color. We shifted to screening a higher socioeconomic status group of our patients and less screening of the lower SES. It was right in front of our eyes as we measure this, as we reopened. We realized because we were studying it carefully, we were leaving a lot of women behind. We’re very concerned because across the country studies are showing that fewer women were diagnosed with breast cancer in 2020 than any other year before. Those women are there, they just haven’t been diagnosed. So we really need to think about what will it mean to recover in the breast cancer domain from COVID? What does that mean? How do we measure it? It’s really critical to continue to be screened during this time because we could be working our way out of this for some time. Well, I think so and I think it’s important that when we do, breast cancer will still be there just as you said and progress in breast cancer is still going to be critically important.
Dr. Garber: So, Connie, other technologies that I’m sure they can all be enhanced by AI, but what can we be looking for that’s maybe a little closer a little more broadly.
Dr. Lehman: Well, I think one of the expressions I always think of is the choose wisely. When we’re thinking about the imaging tools that can improve the outcomes for our patients, how can we choose wisely? And what does it mean to use wisdom? As we make choices about our imaging tools. We’d like to keep radiation as low as possible. We want the sensitivity that the ability to detect cancers to be as high as possible. And we really want to reduce false positives. We have to think about access. Is this something that women will be able to engage in and we have to think about costs. So a huge part of my career was focused on MRI. I was excited because we know vascular imaging, being able to see blood flow in the breast tissue is essential to detect the most number of cancers early, but MRI has so many problems. It turns out that very few women globally, very few women in the US, have access to breast MRI. And that’s a significant problem. And one that even with abbreviated MRI, even with fast MRI, we’re not going to be able to tackle. Contrast-enhanced mammography has fixed the bill of what we need in vascular imaging, but accessible at reasonable cost and still keeping radiation quite low. So this is the type of approach I’m hoping more and more we take in radiology is to really be thoughtful. I would say though, as far as what I’m really most excited about is about this time in history where we’re living now, The Winston Churchill quote, “Never let a good crisis go to waste.” I am seeing so much good come out of the challenges we’ve been through. People wanting to approach problems in a more collaborative way, thinking of all the different culture sets that the BCRF has established for us. Can we think differently? Can we work together? Can we do things faster than maybe traditional methods would have led us to believe we could do.
Dr. Garber: Lisa, we’ve seen new drugs in breast cancer over the last few years. We have challenges to go as we had before for triple-negative disease and metastatic breast cancer and lots of opportunities. What are you most excited about? What do you want to see us be working toward?
Dr. Carey: The direction for breast cancer improvements in care fall in sort in three arenas: one is an expansion of available drugs and all of the drugs that are coming out now are to one degree or another targeted, right? They are leveraging our increasing understanding of biology to develop drugs that themselves are specific for particular subsets of breast cancer. Now we have to use those tools that Connie was referring to, to try and also identify the relevant biology to attach to the drugs. And those two things have to happen together, right? Otherwise, it doesn’t work. But that’s where all the initiatives, including several that BCRF is supporting, to examine the biology underpinning primary breast cancer, metastatic breast cancer, differences and targetability within those two domains is usually important. And I’m super excited about the fact that these are initiatives that are just, their trajectory has been great and they’ve been generating, generating, generating so much enthusiasm and a whole bunch of people, for example, AURORA, which is multiple institutions working together trying to answer these questions.
Dr. Garber: So thank you so much all of you for this rich conversation. And I really do appreciate the fact that you’re here and that we should tell everyone that you are three among 275 investigators that BCRF supports and any one of them could come and tell you about how excited they are about their work and what the impact is of BCRF dollars. So we’ve just had three stars today. As the highest-rated breast cancer organization in the country, and the largest private funder of breast cancer research and metastatic breast cancer research in the entire world, BCRF has a huge impact. Each and every one of us is laser-focused on our shared goal which is zero lives lost to breast cancer.
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