Top Breast Cancer Research at ASCO 2025

This podcast episode is made possible by Lilly. 

Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor, Jamie DePolo.

Jamie DePolo: Hello, I’m Jamie DePolo, senior editor at Breastcancer.org. I’m podcasting live from the 2025 American Society of Clinical Oncology annual meeting. I’m joined by Dr. Eleonora Teplinsky, a board-certified medical oncologist who specializes in breast and gynecologic oncology. She is head of breast and gynecologic medical oncology at Valley-Mount Sinai Comprehensive Cancer Center in Paramus, New Jersey, and a clinical assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York. 

She is also the host and creative force behind the INTERLUDE Podcast, which shares the stories of women who have been affected by cancer. Dr. Teplinsky also serves as an ASCO expert. She’s is going to discuss some of the most applicable breast cancer research presented at this year’s conference. 

Dr. Teplinsky, thanks for joining us. And there have been several studies on breast cancer that have got people talking, so what’s your take? 

Dr. Eleonora Teplinsky: Well, thank you for having me. I’m really excited to be here. So, we’ve seen really three pivotal trials, all in metastatic breast cancer, at this meeting and there are still things for early-stage, some will be coming out later today, but I really think it would be a great idea to highlight the three metastatic trials.

And what’s amazing is that at this meeting we actually have a trial for triple-negative, hormone receptor-positive, and HER2-positive, so one for really each major subtype. So I think we could start with the SERENA-6 trial. 

So, the SERENA-6 trial was presented yesterday as a plenary session, which is kind of the, you know, one of the big, big studies selected for this meeting and also published in The New England Journal of Medicine, and what this study does, it’s for patients with hormone receptor-positive, HER2-negative — and that includes HER2 low because that’s been a question that comes up — first-line meaning first treatment in the metastatic setting, patients who are on a CDK4/6 inhibitor and an aromatase inhibitor. 

And after being on that regimen for six months, what they started doing was doing blood tests to look for ESR1 mutations, and these mutations are, really they emerge with treatment, they’re not present initially, and they are a sign of resistance to aromatase inhibitors. And so, they would test every two to three months, and they tested over 3,000 people, and they detected mutations in a little over somewhere around 550 patients. And then about 350 were randomized to either, so if they detected a mutation that’s a sign, well, maybe the aromatase inhibitor is not going to work in the future. 

So they scanned them and there was no sign of imaging progression. And that’s a really important point because normally we don’t make any changes until we actually see something on a scan. And so, these were patients who had no radiologic progression, and so half of them were randomized to stay on what they were doing: The aromatase inhibitor and the CDK4/6 inhibitor, and the other half were randomized to continue on the same CDK4/6 inhibitor but to switch, so to stop the aromatase inhibitor and switch to camizestrant. 

Camizestrant is an oral medication, it is a SERD, it’s a selective estrogen receptor degrader, and it can overcome these developing ESR1 mutations. And in that group that they randomized, what they found, was that they looked at progression-free survival, meaning time without disease progression or death, and they found that it increased in the group that switched, okay?

So, in the group that stayed on, the average progression-free survival was about nine months and in the group that switched, the average progression-free survival was 16 months, okay? And that translates to a 56% reduction in the risk of progression or death, so exciting.

We can talk about some of the concerns about the study, okay?

So, the first concern is, first of all, camizestrant is not yet FDA-approved, okay, so this is not something that we are going to go do in the clinic tomorrow, okay? Other concern is, well, people were on, they, they were, they had to have been on their treatment for about six months before they started doing the tests, but average time that people were on was about 23 months before they actually, median time. But you know the tests are every two to three months, who was going to pay for the test?

Jamie DePolo: That’s actually my question because if these tests aren’t normally done this frequently, and the tests are kind of expensive, this is very exciting, but are people going to be able to get these tests that frequently outside of a clinical trial?

Dr. Eleonora Teplinsky: And I think that’s a really important question and a big concern. Now, in this study, of course, the tests were paid for. The thought is that if camizestrant gets FDA-approved, that the tests would kind of be a companion approval, but we don’t know, and just because something’s approved doesn’t mean that insurance is going to pay for it. And again, in the study, they did it every two or three months, but is that the cadence? Could you do it every four months? Could you do it, you know, we just don’t know and I think that’s going to be a really big concern. 

You know the other concern that’s been raised is that, and a very, very important concern, is that we don’t have overall survival data, you know, meaning are patients really going to live longer as a result of switching or are we just switching earlier but it doesn’t make a difference in the long-run?

And we also don’t have the progression-free-two survival, PFS-two data, which is kind of what happens at that second progression, because if they switch, let’s say they stayed on their aromatase inhibitor and then they developed disease progression in a scan and switched at that point, right, we just don’t know what that looks like. So, I think it’s really, really exciting, but it’s not, it may, you know, it may be practice-changing in the future, but it’s not right now. 

One, it’s not FDA-approved, we don’t know when that will happen, and there still remain some additional questions about survival and what that looks like after progression.

Now, camizestrant has some side effects and I think that’s also an important point. It can cause some low blood counts, anemia, joint and back pain, a little bit of nausea. There are some side effects of dry eyes and photopsia, which is kind of seeing flashes of light, and slow heart rate. So, again, you know, we know that some patients do really well on their aromatase inhibitor and some people have side effects. So, I think what will happen in the real world, too, will be interesting, you know, once the drug gets approved. So, super exciting, a lot more to come. 

Jamie DePolo: And then there was another trial that I believe is going to be presented today, or I guess I’ll ask you, which next one you want to talk about. I feel like there were three or four.

Dr. Eleonora Teplinsky: Yeah, so we can talk about DESTINY-Breast09 and that was presented actually like half an hour ago, so. But what DESTINY-Breast09 did, so this was a study for HER2-positive, okay? First-line metastatic HER2-positive breast cancer. And so, the standard of care for metastatic HER2-positive breast cancer right now is a taxane chemotherapy, so either Taxotere or Taxol, with Herceptin and Perjeta. And that has been our standard of care since 2012, so for 13 years we have had none. 

And typically what happens is you are on your, it’s called THP, and you’re on that for a certain amount of time, you know, about six cycles, more for some people, that’s individual. And then they could drop the taxane if your scans look good, continue on the Herceptin and Perjeta, and if you were estrogen receptor-positive, you know, we typically add the endocrine therapy. And at the San Antonio Breast Cancer Symposium in 2024, in December, we saw the results of the PATINA study, which actually looked at adding a CDK4/6 inhibitor to your endocrine therapy and your Herceptin and Perjeta, so it’s really an evolving space. 

Now, in second-line therapy typically we now use T-DXd or trastuzumab deruxtecan in HER2, and there’s also tucatinib, capecitabine, Herceptin, you know, it’s a whole field. But what DESTINY-Breast09 did, it said, well, what if we give T-DXd as first-line? Will that improve outcomes? So, it’s a three-arm study, its T-DXd alone, T-DXd with Perjeta, or THP: taxane, Herceptin, and Perjeta. Today, they did not present the T-DXd-alone arm, so we’re not going to talk about that, but they presented the first result from the T-DXd with Perjeta versus THP. 

And what they found was that you know the study met its primary endpoint, meaning giving T-DXd with Perjeta improved progression-free survival, okay? The progression-free survival, again time before disease progression or death, was 26.9 months in the THP arm and 40.7 months in T-DXd. So, it improves it by about 14 months, translating into about a 44% reduction in risk of progression or death. So, obviously, okay, again exciting, exciting, right, but let’s think about that for a second.

The big thing is, now the standard is we drop the taxane chemotherapy, that’s where the side effects come from. Herceptin and Perjeta, certainly, you know, we monitor the heart, and it can cause some diarrhea, but in general people do really well on Herceptin and Perjeta alone. And in this arm here, they stayed on T-DXd with Perjeta, you know, indefinitely until progression, and T-DXd, very effective drug, but it comes with side effects, and so I think that’s the, the balance. 

You know, one of the side effects of T-DXd is interstitial lung disease, pneumonitis, inflammation of the lungs, and it occurred about 12% in the study, which is consistent with what we’ve seen with prior studies. But you know people do have fatigue and they have GI side effects. And so, one of the questions that was raised in the discussion is, what is this going to look like, right? And is it for everyone? Do we select, is there a specific population that we give that to? Is there going to be a point where we can kind of drop the T-DXd and do a maintenance approach? And there is going to be a study that is going to look at that.

So, there are still a lot of questions that have been raised and will need to be answered, but you know potentially practice-changing, and I think it’s really going to evolve. You know, we just saw the data presented, so I think it’s going to really evolve. 

Jamie DePolo: Let me ask you this, so it’s the Enhertu, in a sense, or T-DXd, is kind of taking the place of the chemotherapy in the THP regimen because, you know, Herceptin and Perjeta are there. Now, you can get an injection of Herceptin and Perjeta, Phesgo the brand name, which is a lot faster and easier for people. So, is there any idea that they would look at, I don’t know, all the ins and outs of the study, but say somebody finishes Enhertu, or they stop Enhertu, could they go to Phesgo that way? Or is that just too much Herceptin? 

Dr. Eleonora Teplinsky: I think that’s a really great question and that’s actually, I mean, I think that’s the big thing that was raised is, what if we do T-DXd with Perjeta kind of induction and then followed by maintenance Herceptin and Perjeta? And that is going to be, there is going to be a study called DEMETHER, I may not be pronouncing that correctly, but that’s exactly what it’s going to look at. So, it’s going to look at an induction of T-DXd with, I think just with T-DXd and then Herceptin and Perjeta. 

So, yes, because I think what you raise is a really important point is it’s really about quality-of-life, right? We want patients to live longer, but we also want them to have a really good quality-of-life while they’re living. And so, I think it raises the question of all right, well, what is that going to look like, not just in terms of side effects, but time in the infusion chair, time in the infusion center, coming to appointments? You know, so, and more toxicity, right, and more toxicity and side effects lead to impact on quality-of-life every single day, so there’s still a lot to be answered.

And what will happen in clinical practice, you know, again this is going to really develop and we’ll see how people do. What is interesting is that they did have about doubling of patients who had a complete response. It was about 15% with T-DXd and Perjeta compared to this like eight-something percent, but that raises the question of, well, if those patients have a complete response what, how long do, what do we do, right? 

Jamie DePolo: Yeah, what do you do? 

Dr. Eleonora Teplinsky: What do we do? And do you need to continue? Can you switch? So, there’s a lot of unanswered questions, but I think, again, it’s a step in the right direction. Keep in mind, we have not had any change really since 2012. And then again, how do we integrate the PATINA trial with the addition of the CDK4/6 inhibitor? How do we integrate endocrine therapy? And then another point that was really raised is that, you know, patients who had, previously had early-stage breast cancer and had developed metastatic disease, a lot of them didn’t get all the treatment that we give now. And partly, depending on where they were, you know, and things like that, but would that skew the results? 

So, you know, this is where real world studies become really important about and you know once data is presented people will do real world studies to see, well, what happens outside of a clinical trial? And that’s really important because in a clinical trial everything is very controlled and we know that in the real world, you know, it’s different, so we’ll see.

Jamie DePolo: Absolutely. And then the one final study on metastatic triple-negative, if you want to talk about that, and I don’t, I’m spacing on the name because there have been so many studies. 

Dr. Eleonora Teplinsky: I know, I have to constantly all right let’s remind ourselves of the study. And it’s just, I mean, I really think it speaks to how much is changing, right? Usually, we get one study, and here we’re like, all right, we have so many to talk about.

But this is the ASCENT-04 trial, okay? So, this is for metastatic triple-negative breast cancer that is PD-L1 positive, okay? So, let’s talk about what the current standard of care is. So, if someone has metastatic triple-negative newly-diagnosed metastatic disease, we test for PD-L1. That is a marker response to immunotherapy and if you are PD-L1-positive you would get chemotherapy with immunotherapy with pembrolizumab or Keytruda. If you are PD-L1-negative you get chemotherapy alone. 

Now, there is a number of ongoing trials in this space, so that’s important, but what ASCENT-04 did was, if you were PD-L1-positive either you did Keytruda with chemotherapy or Keytruda with sacituzumab govitecan, which is Trodelvy, and that is an antibody drug conjugate that binds, the antibody, binds to Trop-2 and then the cytotoxic drug that it releases is SN-38, which is a cytotoxic chemotherapy. So, in this study, again, patients got Trodelvy and Keytruda or Keytruda with chemo, and what they found was that there was an improvement, again, in progression-free survival, time without, time until progression or death, for 11.2 months with the Trodelvy and Keytruda versus 7.8 months in the chemotherapy arm, so that’s impressive. 

In triple-negative that’s really important, translating, again, to a 35% reduction in the risk of disease progression or death. They had higher response rates. They had more durable response rates with the Trodelvy and side effects were really consistent with what we know. And this is one where mostly people agree, you know, or people are agreeing that this is going to be practice-changing. 

You know, I think the other studies have some more questions, but here, you know, we know we need better outcomes for metastatic triple-negative breast cancer and anything where we can get a more durable response and a better response in first-line setting is going to be, so I think this is something that, you know, what we’re going to do in the clinic.

Jamie DePolo: Like, going home tomorrow.

Dr. Eleonora Teplinsky: Going on home tomorrow, yeah, we’re going to talk to our patients about that. And of course we’ll manage the side effects, but this is one where we really want to get our sustained response in triple-negative breast cancer. So, I think all of them certainly, I think the other two, you know, potential to be practice-changing, but I think this one is something that most of us are going to go home in the clinic and implement. 

Jamie DePolo: Let me ask you one question. Iis there any concern, like, if this specific indication isn’t FDA-approved is that an issue at all or can you just start using it in that way?

Dr. Eleonora Teplinsky: And this is, this is a great question and it always happens, you know, we get these major study presents, studies presented and well what is insurance going to cover? Because right now the FDA label for Trodelvy is after two lines of chemotherapy and so it’s going to vary. I do not know how insurance will react to this study. You know, we can quote the meeting and quote the results, and it’s going to be tricky, and I think it’s going to be variable, and it’s going to really require us to fight for our patients. 

I’m hopeful that the FDA indication will change based on this study, sometimes guidelines get issued and that can help us advocate with insurance companies, but that is a big, that is a big concern, and I think we won’t know until we start to use it to see what happens. 

Jamie DePolo: Dr. Teplinsky, thank you so much. I appreciate your insights. This has been very helpful. 

Dr. Eleonora Teplinsky: Thank you for having me.

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