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BCRF Investigators Discuss Breast Cancer Developments at Annual Symposium

By BCRF | December 10, 2020

Hear from four researchers on this special edition of our podcast

Each October, BCRF-funded investigators are honored at the Foundation’s Symposium & Awards Luncheon in New York City. This year, the program was held virtually, without the lunch—but with all of the important conversations and ideas.

The annual event announces the Foundation’s grant investment for the coming year and recognizes BCRF investigators for their trailblazing scientific inquiry. It also provides a rare and unique opportunity for BCRF researchers to come together to share ideas and collaborate with fellow colleagues from around the world. About 215 of BCRF’s 275 researchers attended the live, online event.

This year’s program included an extraordinary symposium, moderated by BCRF Scientific Director Dr. Judy Garber, that included:

  • Dr. Angela DeMichele from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center.
  • Dr. William G. Kaelin, Jr. from the Dana-Farber Cancer Institute. Dr. Kaelin is the recipient of the 2019 Nobel Prize in Physiology or Medicine and was honored with BCRF’s 2020 Jill Rose Award for Scientific Excellence
  • Dr. Lori J. Pierce from the University of Michigan. Dr. Pierce is a member of BCRF’s Scientific Advisory Board and the 2020 American Society of Clinical Oncology president.

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

Read the transcript below:                 

Chris Riback: This is a special bonus episode of Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation [featuring] conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship, and metastasis.

The panel was moderated by BCRF’s Scientific Director Dr. Judy Garber of Dana-Farber Cancer Institute.

We’ll have our regular episode of Investigating Breast Cancer in the next couple of weeks. Now, here is Dr. Judy Garber and BCRF’s 2020 Symposium.

Dr. Judy Garber: Hello, and welcome to the 2020 BCRF Symposium and what would ordinarily be the luncheon. I’m Judy Garber. I’m the scientific director of the Breast Cancer Research Foundation, and I’m a breast oncologist and cancer geneticist at the Dana-Farber Cancer Institute in Boston. It is our privilege today to have three investigators join us here to talk about breast cancer, progress in breast cancer, challenges in breast cancer, how are we living with COVID, and to bring us really to the frontlines of progress in this important field.

So Dr. Angela Demichele, from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, Dr. William Kaelin, who is the winner of the 2019 Nobel Prize in Medicine, from the Dana-Farber Cancer Institute in Boston, and Dr. Lori Pierce from the University of Michigan, who is this year’s president of the American Society of Clinical Oncology. So, Angie, would you like to tell us a little bit about yourself and your work?

Dr. Angela Demichele: Thank you so much, Judy. It’s really a pleasure to be with you all today. So I am a medical oncologist, I trained in clinical epidemiology and clinical trials. And so I do some clinical care and a lot of clinical research. I work both within my own group doing original research, but also within several different consortia. I co-chair the breast committee on one of our cooperative groups, the ECOG-ACRIN group, and I work in several other large groups.

Dr. Judy Garber: Thank you. Bill?

Dr. William Kaelin: So I’m also a medical oncologist by training, but in the ’90s, I pivoted towards laboratory-based research. I try to understand the functions of specific genes, particularly genes that are mutated or altered in various cancers. And I try to use that information to develop better therapeutics. And in that regard, I work with a number of both pharmaceutical companies and biotech companies to try to use laboratory-based knowledge to help create the next generation of cancer drugs.

Dr. Judy Garber: Thank you. Lori?

Dr. Lori Pierce: And I am a breast radiation oncologist, and I focus on clinical research and clinical medicine as well as translational research. And our research as of late has really been focused on those tumors that tend to be more difficult to control, following standard therapies, lumpectomy, and radiation. And so we’re really focused on how best to select those tumors and what strategies we can use to overcome radiation resistance.

Dr. Judy Garber: So you can see that everyone is extremely well qualified to answer our questions today, and to tell us all about what’s happening in breast cancer and what’s going to be happening in breast cancer. So, Bill, let’s start with you. The Nobel Prize, it is the prize. It’s a huge deal. And I think everyone is always excited to hear about the work that actually led to the prize for you. And a little bit of the impact of that work has had on cancer research.

Dr. William Kaelin: Yes, thank you, Judy. So I shared the prize with Gregg Semenza and Sir Peter Ratcliffe, for the work we did that allowed us really, for the first time, to understand how the cells and tissues in your body sense how much oxygen they’re getting. And if they’re not getting enough oxygen, to then respond appropriately, to survive in a, for example, low oxygen environment. This turns out to be very important for cancer because cancers are constantly facing a battle, trying to get enough oxygen to allow them to grow and to spread.

So now that we understand the molecular circuitry, if you will, that controls this response, we now have newer drugs being developed that, for example, can prevent the cancer cells from getting enough oxygen. And hopefully, stopping them in their tracks. But there are also some other new drugs that are helping patients make their own red blood cells based on this knowledge. And that might be useful for people who are developing anemia as a result of chemotherapy treatment.

Dr. Judy Garber: It’s so wonderful to hear you make it something that we can all understand. But it’s hugely important. No one doubts the importance of oxygen. Lori, so the breast cancer community, like our national community, has really begun to grapple with issues of racial and ethnic disparities, and justice in our own world. And you have made this a centerpiece of your ASCO presidency, which is quite a big pulpit. Can you talk about this issue for us and educate us on what we should know and what we should be thinking about from BCRF and beyond?

Dr. Lori Pierce: Sure, I’m happy to. So as you mentioned, I was honored to have been elected president of ASCO. And when you’re elected, as you probably know, you get to pick a theme. And so a year and a half ago, I picked the theme of equity of care because equity has always been so very important to me. As an African American, I’m acutely aware of the disparities for people of color. In almost any metric, no matter what you look at, people of color do less favorably. And certainly, cancer is no different. And so I knew I wanted to pick equity as my theme. And so my theme is equity; every patient, every day, everywhere.

And of course, since that time, equity, or I should say the lack of equity has been front and center for all of us in this country, in the world. And there has to be change now. So I think we all need to have a vision. I think we all need to have a plan for change. And so, what is my vision as being ASCO president? If you provide equitable care, you decrease the disparities that exist. And some of the disparities are due to social determinants of health, like where people live, their level of education, where they work, their financial resources. And it’s hard for us to directly impact those. But we can impact how we give care, and that is equitable.

And so much of what ASCO was doing already was focusing on so much of what BCRF does, is absolutely consistent with that. So some of the initiatives that we’re doing at ASCO, we are focusing on clinical trial participation, because we know that underrepresented minorities are underrepresented on clinical trials. And we have an initiative with the Association of Community Cancer Centers, ACCC, that’s also focused on equity and bringing minorities in clinical trials. We’re working on that together, and so that’s a very exciting initiative. We’re learning more about social determinants of health, and we’re doing that in a space to educate our fellows and our junior faculty, because they are the leaders of oncology tomorrow.

And we’re also focusing on bringing more providers of color, and bringing more students of color into oncology because we know that African American and Hispanic providers are truly underrepresented. And perhaps, patients of color would feel easier interacting with providers of color. And to that point, BCRF is working with us on that. The BCRF funding that goes to the trainees for Conquer Cancer, ASCO, will now be dedicated to disparities research. So all together, we are collectively working together to decrease disparities and improve our patient outcomes.

Dr. Judy Garber: That’s great, Lori. That is a huge undertaking and a task that’s certainly worthy of all of the attention that you’re giving it. Thank you. Angie, you have taken on a very difficult part of breast cancer care in the treatment of metastatic disease, which is so challenging, trying to prevent metastatic disease and then trying to manage metastatic disease. Do you want to talk to us a little bit about your thoughts about where we are and what you are finding most exciting at this time?

Dr. Angela Demichele: Yes. Well, Judy, we’ve made so much progress in the last 40 years in our therapies for newly diagnosed breast cancer. And that’s led to many women being cured of their disease. But as any woman who’s been diagnosed knows, there’s a lot of activity initially to take care of that cancer when it’s first diagnosed; surgery, chemotherapy, radiation. And you get to the end of that. And the hope is that you’re cancer-free. However, I think as a practicing medical oncologist, sitting with women who are at that stage of treatment, there were so many questions.

How do I know that the treatment worked? And how do I know if the cancer will come back? And I think what’s really exciting is that the laboratory scientists have really taught us a lot in the last, I would say five years about what it is that actually leads to a recurrence. So we now know that there are very specialized cells that can leave the breast, that are resistant to those initial therapies. These cells can travel in the bloodstream and ultimately, make their way to the bone marrow, where they can essentially go to sleep. And these sleeper cells can stay there for months or years, or even decades. But something then causes them to awaken and to travel to other parts of the body.

My research is part of a translational center of excellence, which means that I work in translating that work from the basic scientists in the laboratory who have figured out these mechanisms, to then try to bring that into the clinic. We can do that now with some new technologies that enable us to measure the fragments of tumor DNA in the bloodstream to let us know if there are still microscopic cells around. We can also look in the bone marrow to see if those cells, those sleeper cells are there. And working with my partner in this effort, Lewis Chodosh, we’ve identified several different drugs that can actually attack the sleeping cells.

Those cells aren’t dividing, and so they are very different than the typical breast cancer cells that are in the breast when you’re diagnosed. They need different drugs. And so the laboratory work that actually was funded by BCRF and Dr. Chodosh’s lab, to help us identify some of these new drugs, now is funding a clinical trial BCRF is supporting, where we’ll be screening women who have finished all of their treatment, are now a couple of years out from finishing that, who will have a sample of bone marrow taken to look for the sleeper cells. And then if those cells are there, we have the opportunity to give these women treatments. And these treatments vary from drugs that will attack the cells themselves, but also we’re looking at how we can help the immune system actually recognize that the cells are present.

Because ultimately, it’s a failure of the immune system to clear these cells. And so new immunotherapy approaches give us the opportunity to help the immune system recognize that these microscopic cells are there. And hopefully, clear them from the system before they ever can cause a recurrence or a metastasis. That ultimately, I think for many of us, feels like the last frontier in terms of how we can close that gap and ultimately, cure every woman who is diagnosed with the disease. And it also gives us an opportunity to develop tests that can help us to monitor a woman who’s had breast cancer.

So rather than simply wondering if this is going to come back, ultimately, we would love to have the ability to look for these cells, so that when you come into the doctor’s office, there’s a test that you can do that would help us know. Do you have any cells around that we could take care of? And that’s a much more proactive approach than what we currently have available. Much of this is still in the investigational phase, but I think it’s wonderful that BCRF has recognized how important this is, and is funding research in this area in many different laboratories and clinics around the country.

Dr. Judy Garber: Thank you. That certainly is exciting, and we are thrilled to be part of it with you. Lori, what’s going on in radiation oncology? And what’s new and you think will impact our high-risk patients?

Dr. Lori Pierce: When we generally treat patients following lumpectomy, we treat the whole breast with radiation. And then for those patients who would benefit from an additional boost, we give a boost to the tumor bed. But we’ve learned through the years that the outcomes are exceptionally well, particularly in some patients to the point that we may be treating too many patients. There may be a way to select those patients that perhaps, would do well. And be safely treated just with the surgery and systemic therapy, and not need radiation.

Because radiation, while it’s well-tolerated, there are side effects. And so if you can minimize the side effects by being clear for who needs to be treated and who doesn’t, then it’s great for all of us. So there are trials that are currently ongoing in the US and in other countries, including Australia as well, where patients with small tumors that are estrogen receptor-positive, that do not have lymph nodes that are involved, very favorable patients, particularly in postmenopausal patients, where we then use perhaps Oncotype, or other ways that we can discern those tumors that again, have a really, really good prognosis.

And we are omitting radiation. And we’re following them very carefully, to see that if with those selection criteria, we can arrive at a group of patients that will be successfully treated even in the absence of radiation. Just recently, there were two large trials, one from Florence and then a really large trial from the US, looking at patients getting whole breast radiation versus others just getting partial breast where just a portion of the breast is treated. And the recurrence rates at 10 years were less than 5%. So clearly, that is a group of patients that we know that are successfully treated with just treating a portion of the breast, and not the whole breast. And that leads to fewer side effects.

And then for those patients who do require whole breast treatment, we’re learning a lot about if we can shorten the treatment, giving more dose per day, but giving fewer days of treatment called hypofractionation. And we know from many scientific trials that you absolutely indeed can cut down the duration of treatment from the typical six weeks to four weeks. And now, with trials that just got released recently, there’s a trial from the UK showing you can give one treatment a week for five weeks, and have the same outcome as those who had the longer treatment. And that was 10-year data.

And then yet another trial from the UK showing that you actually can use five days, successive days, and treatments and have the same outcome as longer courses. And that, we have five-year data for. So there’s a lot of flexibility with how we can treat patients. And basically, we’ve got a toolbox now. We’re not treating everyone the same. We can help to identify those patients by their cancers that can have a range of options, and work with patients to figure out the best treatment for them.

With regard to high-risk patients, that actually gets it some of the research that we’ve been doing. And my partner in research is Dr. Corey Speers, an exceptional radiation oncologist, also here in Michigan, who has also been funded through BCRF. And we have looked at whether we can develop gene expression signatures such as what medical oncologists have been doing for so long, to help pick those tumors that are well-controlled with radiation. And those for whom, maybe more radiation or other options are necessary because they aren’t well-controlled with standard radiation. And so we’ve been looking at developing these signatures, and then also coming up with strategies for how best to intensify treatment.

For many years, I’ve been interested in this. And many years ago, I did a study with gemcitabine, chemotherapy, and radiation, because gemcitabine was known to be an agent that helped to sensitize the tissue. So you get more effect from the radiation to overcome the radiation of resistance that we see in a select group of tumors. And sure enough, the combined treatment was great with 100% tumor control, but the side effects were pretty significant. So even though the patients that were treated in the study said, “Oh, it’s okay, it’s okay because the tumor is gone away,” it wasn’t okay to me because I knew that there had to be ways to have more targeted therapies, that we could achieve excellent to control and not have the side effects.

And so subsequently, we have worked on PARP inhibitors and added radiation. Actually, an interesting story, and I’ll be very brief. I had just gone to a meeting at Oxford. I wanted to bring the PARP inhibitors into the radiation space for breast cancer. And so at that point, I said that we need to set up experiments, and I brought in Dr. Speers when I got back to Michigan. So we had to have experiments to show us how best to do this, and whether or not my hypothesis is correct that it really will sensitize tumors to radiation. And so thanks to BCRF, we were able to do these experiments. And sure enough, we found that sensitization, which we then carried to a phase one trial, which was also funded by BCRF. So we were able to show that indeed, PARP inhibitors and radiation, they were a very good combination. And now, thanks to all that preliminary work, there is now a national randomized trial, looking at adding PARP inhibitors to radiation. And none of that would have been possible without the BCRF.

And then finally, we are now looking at hormonal therapies with radiation, androgen receptor. We know that through preclinical information, data, that if you inhibit those androgen receptors with drugs that are readily available, and very well tolerated, that you overcome radiation resistance. And so we’re now looking at that. And that’s very important because androgen receptors are in all tumors, including triple-negatives. And so this may be a way of having yet another piece in armamentarium against triple-negative breast cancer. So there’s a lot going on right now in the radiation space. I’m so glad you asked.

Dr. Judy Garber:  So Bill, as the representative of the basic science community here, what are you finding the most exciting?

Dr. William Kaelin: Great question, Judy. So first of all, as you know, scientists are notorious for using their own private jargon. So I’m going to demystify a couple of things. The first is when a scientist talks about a gene, of course, a gene to a first approximation is a set of instructions for making a particular protein. So for example, gene A contains the instructions for making protein A, gene B contains the instructions for making the protein B, etc. Now, this is important because the question that our colleagues in the pharmaceutical industry and biotech industry are always asking, if we can make a new drug for breast cancer, should it be against protein A, should it be against protein B, et cetera? That’s really the job of the basic scientist, is to try to help them understand, what are the so-called targets they should be going after to develop their new drugs?

So I’m tremendously excited because as you know, for the past 20 years, we’ve had to first approximation, the identities or sequences of all the genes. But that of itself doesn’t help us very much. We have to understand the functions of those genes, and we have to understand which of those genes are altered in specific cancers. So an analogy I like to use is tumblers on a lock. You can think of any given tumor as a lock that had several tumblers, with each of those tumblers being an alteration in a different gene. And it was only when the right combination of genes were altered, that that cancer could evolve.

So now, as you know, with rapid advances in sequencing, for the first time, we can fairly quickly look at a particular tumor, find out exactly which genes had been altered, what were those tumblers, if you will, that led to that particular cancer, which really helps us inform a precision medicine approach of matching the right drug with the right tumor. Or put another way, with the right patient. Secondly, we have much more powerful tools now for identifying in the end of the day, which genes does a particular cancer care about the most for its survival? We sometimes refer to these as dependencies. And again, that’s incredibly valuable information for our colleagues in the pharmaceutical industry.

And so when thinking about it, I think it took literally decades to figure out that at least a subset of breast cancers cared deeply about the estrogen receptor, which of course, is the target of tamoxifen. With today’s technologies, you would have figured that out in less than a week. So I think that gives you some sense of how quickly things have changed. That’s partly because of a new technology called CRISPR that some of the members of our audience might have heard about, which allows us with really unimaginable precision, to go in and alter specific genes to begin to understand, first of all, what their normal functions might be. But secondly, to find out again, whether certain cancers depend on those genes. That’s revolutionizing our ability to identify potential new targets and various cancers, including breast cancer. And to try to take some of the guesswork out of drug discovery.

When I was starting out, a lot of drugs were discovered by sprinkling them on cancer cells and hoping some of the cancer cells died. That was a relatively blunt approach to developing new drugs. Now, we can really put forth to our colleagues in pharma, a list of experiments that gives them great confidence that were they to make a drug against this particular protein, it would have the desired outcome. Namely, to stop the growth of a particular type of cancer and potentially, breast cancer.

So I think we’ve come so far, to summarize in terms of our ability to know which genes are defective in different cancers, and to begin to understand the functions of those genes. And to understand which of those genes would be perhaps, most fertile for future drug discovery. So I think all of these things are incredibly exciting.

Dr. Judy Garber: I think where you share your enthusiasm about the fact that we can now, not only in the laboratory, parse out the genetics of the tumors, but the technology allows Angie to take her patients and figure out which genes in this patient are actually driving things. What should the targeted therapy target? And that can be done clinically.

So by the time it gets to a clinical place, it’s been perfected in the lab or adapted in the clinic, and on the tumors and in the cell-free DNA that’s circulating, so that we may not even have to get to the tumor. So here’s Lori’s got us thinking about ways we can cause less harm, or do things in easier ways. Right now, we have to look at the bone marrow. Someday, maybe we’ll be able to find those same cells circulating.

I think the Founders Fund was a place where BCRF said, and Larry said, we have to know about metastatic disease. We have to be able to sequence these tumors. And that’s what that money has been used for. So I think we all share your enthusiasm for that. And that as an example, with CRISPR, for the ways that technology lets us move forward. Angie, with research, where are our best opportunities? And what if we can’t follow them? What’s going to happen?

Dr. Angela Demichele: It’s been an incredible couple of years in breast cancer drug development, in particular. And for women who have metastatic disease, we actually have a wealth of new agents that really came about because of our understanding of the genetics of breast cancer, as Bill discussed. And so we have seen new drugs for HER2-positive breast cancer. We now have a drug called tucatinib that actually can cross the blood-brain barrier and help to treat women whose breast cancer has traveled to the brain. We’ve never had a drug in HER2-positive disease that could do that.

In triple-negative disease, we have the advent of immunotherapy. And we’re starting to finally see some great results in bringing checkpoint inhibitors that have been so successful in other cancers into breast cancer so that we can help the immune system recognize these tumors, and work with chemotherapy to eliminate them. And we have drugs in both HER2-positive and triple-negative disease that are these new antibody-drug conjugates. So we can take an antibody that actually docks to the cancer cell, link it to a chemotherapeutic so that that payload is essentially brought right into the cancer cell.

That’s led to the approval of a drug called Sacituzumab, for triple-negative disease, that has a high response rate. This is the most exciting drug we’ve seen in triple-negative disease for a very long time. We’ve also got that in HER2-positive disease. And actually, we’re now starting to see that maybe even tumors that aren’t covered in HER, aren’t those high HER2-positives. But even tumors that have even less of the HER2 could take advantage of this docking ability from these antibody-drug conjugates. So these are monumental changes that are giving months to years of life to women who have metastatic breast cancer.

And these targeted treatments have much less toxicity than chemotherapy that we used to give in the past. So that although we still have so much work to do for metastatic breast cancer, we are seeing now with these drugs, CDK4/6 inhibitors, others, that we can string these drugs together and give women with metastatic disease, a lot of time, and a lot of really good, quality time. And I fear that if we lose this momentum, we lose this pipeline from the laboratory to the clinic, to ultimately run the trials that are going to be able to show that these drugs can work, and get them out to patients. That we’re going to lose this wealth of knowledge that’s coming out of the lab, and we’re not going to be able to capitalize on that.

And we’re going to really stop this amazing progress that we’ve had with all of these new drugs over the last few years. And it takes time to do clinical trials. And it really takes a lot of infrastructure, which we have built over decades. And so we can’t lose that momentum and infrastructure, because we really will lose the whole next generation of treatments if we can’t keep that going.

Dr. Judy Garber: Lori, what are you excited about? And what are you worried about?

Dr. Lori Pierce: So I am excited about the advances that we’ve made this far, thanks to BCRF and others that have allowed us to treat our patients effectively, and decrease side effects. We know that with radiation, you can improve survival. And we know that with radiation if given the right way, our patients will have long-term tumor control. We know that we have to be very careful, obviously, in how our treatment is given. We must continue to have that forward momentum so that we continue to be even better at what we do. And that we can know when we can safely withhold treatment, and know when we do need to intensify treatment, how best to do it.

Dr. Judy Garber: Thank you. So let’s make a little shift here. We’ve talked a lot about treatment, we’ve talked a lot about trying to optimize treatment and not over treat, which is a great place to be able to think that we might be able to back off on some of these. But one of the wonderful things that lets us do that is that we have a lot of breast cancer survivors.

And of course, women who are surviving, they’re grateful, but many of them live with the long-term consequences of our treatment. And at least one of our audience is particularly interested in what we are doing to think about this challenge. So I wonder if, Angie, if I could start with you? Do you want to speak a little bit toward things that you are aware of, that have really become part of care, and what else we can be thinking about?

Dr. Angela Demichele: Yes, I think we have now recognized that women who are survivors have unique needs, that the experience of breast cancer and its treatment doesn’t end when the treatment ends. And so there’s been a really large effort now to focus on many of these long term side effects, particularly effects to the heart, that both our drugs and radiation can have. So there’s a lot of work now to try to understand whether there are markers in the blood, or even by echo that could tell us whether a heart is suffering effects later on so that we could start to intervene and prevent heart problems for women later on.

We have work going on for this issue of chemo brain that I know so many women really struggle with. And it’s something we don’t really understand very well, whether it’s an effect of the chemotherapy, or maybe in part, an effect of the hormone loss, the loss of estrogen that comes along with our therapies. There’s a lot being done right now to really try to understand this, as well as other side effects of estrogen withdrawal, which I think are the biggest effect on patients’ quality of life. The hot flashes, the joint pain, these are things that I hear day in and day out, that are just so bothersome, so difficult and get in the way of function. And so there’s a lot of research going on.

In fact, last year, we had a wonderful trial showing us that acupuncture could actually, in a randomized trial where half the women got acupuncture, and half of the women got what was called sham acupuncture, actually needles that didn’t really work, but really made the patients feel like they were getting it, it really showed that acupuncture made a difference in some of this long term pain. And so we’re really starting to think about not just drugs, but also alternative therapies that might be useful for these side effects.

And then as Lori touched on, I think the other really important thing is, we’re starting to realize that maybe the best way to take care of these long term effects is to prevent them from happening in the first place, by seeing where we can eliminate some of the most toxic drugs. So Adriamycin, the Red Devil, that drug really has a lot of long term side effects, including heart effects and bone marrow effects.

And now, with these targeted agents that we were talking about earlier, we’re seeing that those agents are so effective. That we may actually start to be able to take away some of the more toxic, less focus, less targeted agents, the chemotherapy, and still see excellent outcomes. And so we launched a trial this year, called Compass that is looking to eliminate Adriamycin from the initial regimen in women with HER2-positive disease. But we’re also looking at this in other subtypes of the disease.

And lastly, I will just say that the other thing that is still on the mind of many women, particularly with ER-positive breast cancer is this ongoing risk of recurrence, as we talked about. We’re starting to think about late recurrence, about what happens after five years of endocrine therapy, of the anti-estrogens. And planning trials that will actually utilize some of these new technologies to help us find women who might still be at risk five or 10 years down the line. And are there agents and drugs that we can use then to help prevent their risk? So things that we can do really many decades beyond the diagnosis that will help quality of life.

Dr. Lori Pierce: Can I add also, one thing?

Dr. Judy Garber: Please.

Dr. Lori Pierce: And that is that, and I applaud the member of our community who asked this question because I think it underscores how important patients are in the direction that research goes. If I had to think about how trials were written many years ago, and I don’t want to date myself, there was not a patient-reported outcome piece. And now, patient-reported outcomes are such an important part of our trials, so that we get that feedback. And we know the issues that really matter to patients. And that clearly, has colored our approach going forward.

Dr. Judy Garber: I wanted to make sure that we got a chance to speak directly to the ways in which COVID, which has changed our lives so much that we’re all here virtually, is affecting our patients and the way we’re thinking about the way we do patient care. And then, Bill, I’m going to ask you to speak about the way the COVID crisis has affected research. So let’s go in the other order this time. Lori, why don’t you start and talk about the ways you’ve seen COVID affect care of oncology patients?

Dr. Lori Pierce: COVID caused a significant change in how we would bring patients in. And we had to, of course, adopt physical distancing and the PPE. And we had to make sure we reassured patients that they were in a safe place, that they could continue to come for their treatments. With radiation, and I mentioned this earlier, we had been before COVID, even focusing then on abbreviated courses of treatment. So that was something that was particularly important to use during COVID. And actually, even beyond. And then we’ve adopted telemedicine far more robustly than what we had before. Radiation oncology, and I think part of the same thing for the other disciplines.

Fellow medicine was severely underutilized. We’ve had to work in this godawful pandemic. There should be something positive that we can take from it, and I think it’s telemedicine, that we can learn how to use telemedicine. Know when the appropriate times to use it, and be able to reach more patients that way than perhaps, we could before. We have to make sure that the playing field is level, that everyone has Wi-Fi, everyone has a way to access it. But with that, I think we will actually be even smarter in how we can deliver care, and certainly how we can do clinical research.

Dr. Judy Garber: Thank you. Angie?

Dr. Angela Demichele: I think it’s really important to recognize, we do things in teams. So we have clinical teams, and we have research teams. And when COVID hit, it really meant that overnight, we had to think about how to do things differently. We do understand now, that patients who’ve had cancer in the past are unlikely to be at increased risk. But it does seem that patients who are actively getting cancer therapy may be at increased risk, particularly if they’re getting very myelosuppressive or immunosuppressive chemotherapy. And so we had to make a lot of changes really quickly. And we worked as teams.

Initially, the operating rooms shut down because there was just too much risk of spreading COVID. So women who typically would have gone to surgery, all of a sudden, we needed to switch gears and start with chemotherapy. But we knew we could do that safely because we had trials that told us that it was okay to give the chemotherapy first, and then do the surgery. And so we were able to adapt by working as a real team on the clinical side, to find ways that we could do things safely for patients, minimize their risk, space out the time between doses, use boosters like the growth factors to make sure the blood counts didn’t get too low.

And really, help women get through this. Because clearly, breast cancer wasn’t going to stop just because COVID hit. And we really needed to make sure and continue to work really hard to make sure that COVID isn’t in any way negatively impacting how well we can take care of patients. We just don’t want any woman to have her therapy compromised, or her outcome really compromised by this pandemic, if we can help it.

Dr. Judy Garber: Thank you. And I think as you said, we don’t want women also to stop going for mammograms, or to stop being diagnosed early. If you feel something and you’re worried about it, don’t stay home and wait. There’s no reason. The hospitals and clinics are not unsafe places to go and get care. Waiting might be.

So I would use this time to say that when COVID is gone, breast cancer will still be here. And it’s our responsibility to make sure that we are still positioned to make progress against breast cancer. Our patients very much will still count on us to do that. But there’s not infinite money. There’s always going to be an issue.

Bill, what do you think is the most important and most concerning possible place where we really could be hurt, if we are unable to manage to do both, to deal with COVID and to still support breast cancer?

Dr. William Kaelin: I do worry about this next generation of researchers. They’re just getting started. They’re just starting their professional careers, but they’re also often just starting their families. And it’s like we’ve enlisted these wonderful people to join the battle, but I want to make sure they feel like we have their backs and that they’re properly equipped. So I just think it’s so important we remember the young people who we’ve had the good fortune to enlist in this battle against cancer and make sure they’re properly funded.

I couldn’t be more excited about the possibilities if we get this right. We now have this fourth modality, immunotherapy, to add to surgery, radiation, and medicine. And I think we’re in the early innings of what that’s going to be able to do for us. And I think we’re just beginning now, with these new tools, to be able to tell our pharmaceutical colleagues, the next generation of targets should be the following proteins. And if we inhibit these proteins, it’s going to dramatically change outcomes in this disease.

And the final thing I will say that, again, I’m preaching to the choir, we’ve known for decades that to cure a disease as complicated as breast cancer, we’re going to need effective combinations of drugs. Each of which is active in its own right. And each of which has hopefully a distinct mechanism of action. And you can just see it happening. We’re just about to get there. We have some wonderful agents that are now being used as single agents, or not quite yet in the right combination. You can see it. And so I can taste it. I can feel it. I just hope we get there.

Dr. Judy Garber: Thank you. Angie, I’m going to ask you to talk about something maybe you hadn’t planned to. But you talked about working in teams. And teams at Penn, but teams all over. Do you want to talk about collaboration a little bit, something, how you view this as an important factor?

Dr. Angela Demichele: Well, I do think that science has become so complicated. And everything we can do has tremendous potential, but no one person can really do all of the different things that are necessary to identify a target, develop a drug, bring it to patients, and ultimately test it and get it to market. So we have to work in teams because we all have complementary skillsets. And when we put them to work together, we can generate more than we could ever have done individually. And that’s the reality.

And I think that’s why many of us went into cancer research because we actually really enjoy these teams. And I know for myself, that is some of the richest time that I spend is really working with other investigators, whether they’re at my own center or across the country or around the world, really to talk about new ideas. I’m constantly learning. And then really, taking these ideas and trying to bring them to the clinic.

I just want to underscore what you said earlier, which is we figured out how to make the hospital and the clinic a safe place. And we figured out how to work in teams to give patients the best possible care, even with COVID. We really have to be sure that patients are coming, and they know that it’s safe. And they aren’t staying away because they’re afraid.

Dr. Judy Garber: Thank you for that. Lori, I’m going to let you close, and talk about something that you are in a place of leadership in cancer research, certainly in the COVID era. Cancer is not our only concern, but it is one of our concerns. And what I think we’ve heard so eloquently from everyone, are the possibilities that we just try not to let things shut down, we keep going. How would you like to close today, with all that you’ve heard and all the opportunities we have to make progress?

Dr. Lori Pierce: There’s been so much we’ve heard today, and the speakers have been so eloquent. As Angie said, the sum is bigger than the parts. So we all have our areas of expertise, and we bring them together in the best possible way on behalf of our patients. And we need to have continued funding, we need to continue to have that positive momentum. Yes, we all know that COVID was a major bump, but we are recovering. And we are moving forward. And we want to continue that momentum.

We don’t want to lose the next generation of researchers, both laboratory researchers, and clinical researchers, and clinicians. We need to continue to have the funding so we continue the forward movement. So we can continue to do the very best we can for our patients. And so I thank BCRF for all the funding you’ve provided. I thank you, BCRF, for the funding you will provide. We will beat this virus and we will beat this disease.

Dr. Judy Garber: Thank you. I’m sure that everyone would agree that we have more than 200 amazing investigators in BCRF. But we could hardly have done better than the three we’ve had with us today, trying to teach us all about breast cancer, to help us understand where are we going, where do we need to go to make us see that we have tremendous opportunities to continue to move forward.

Our patients expect and demand that we will do that for them, and we all want to. We are always grateful for the opportunities to learn from each other and work together. We thank BCRF for that as well. So thanks for being with us today, and thanks for a wonderful set session today. Thanks to you all.

Outro: That was BCRF’s 2020 Symposium and a special Investigating Breast Cancer podcast. Thanks for listening. To learn more about breast cancer research or to subscribe to our podcast, go to