Front Row Seat: Can We Talk about the Cure? A Conversation with Dr. Eric Winer

For a long time, the word "cure" and "metastatic breast cancer" didn't belong in the same sentence. That's changing — and nobody is better positioned to explain why than today's guest.

Dr. Eric Winer is one of the world's leading breast cancer oncologists and researchers, former president of ASCO, and director of the Yale Cancer Center. In this conversation with Victoria Goldberg, he tackles the question he posed at the 2025 ABC8 conference in Lisbon: Can we talk about the cure?

In this episode:

• Why HER2-positive metastatic breast cancer is the subtype closest to a cure — and what the biology tells us
• The landmark trials rewriting the playbook: CLEOPATRA, PATINA, and DESTINY-Breast09 (DB-09)
• What "curative hope" means and how Dr. Winer talks about it with his own patients
• The truth about comparing DB-09 to CLEOPATRA — and why rushing to make Enhertu the universal first-line standard may be premature
• Oligometastatic disease, cancer dormancy, and surgery in the metastatic setting
• The emerging science of exercise and cancer outcomes — and why it's no longer just about quality of life
• Two groundbreaking curative-intent trials: SAPPHO (Dana Farber) and HERizon-Breast (Memorial Sloan Kettering, now open for enrollment), and what sequential therapy is actually trying to do

This is one of the most substantive, hopeful, and honest conversations we've had on Live from Stage IV — and one we've been waiting a long time to share.

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The information shared in this episode is for educational purposes only and does not constitute medical advice. Always consult your healthcare team about your individual treatment options.

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Until next time, take care and keep pushing for progress.

Transcript

SPEAKER_04 0:09

Could a cure for cancer be closer than you think? Welcome to Life from Stage 4, where MBC takes center stage as we talk to experts, share inspiring stories, break down signs, and shine the spotlight on what matters most. Because when it comes down to it, this part for us and by us is all about us. Welcome to Lives From Stage 4. I'm Victoria Goldberg, and this is Front Row Seat, our special series where we sit down with some of the most brilliant minds in medicine to talk about what's happening right now in metastatic breast cancer research and treatment. Because when you're living with stage four, you don't have time to wait for the headlines. You need to hear it straight from the people who are doing the work. And today's conversation is one I have been waiting to have for a long time. We're talking about something that not long ago felt impossible to even say out loud. The cure for metastatic breast cancer. For decades, a stage four diagnosis meant we were managing the disease, not beating it. But that story is starting to change. And nobody is better positioned to talk about where we are, how far we've come, and what's on the horizon than my guest today, Dr. Eric Weiner, is one of the world's leading breast cancer oncologists and researchers, a former president of ASCO, and a true friend of our community. Let's get into it. And Dr. Weiner needs no introductions, but for that one person out there who may not know who he is, I would like you to tell us a few words about yourself.

SPEAKER_01 2:22

Sure. I have been a breast cancer medical oncologist for a long time, more than 30 years, and a breast cancer researcher. I spent many years of my career up at Dana Farber, where I ran the breast cancer program. And for the past four years, I've been at Yale where I'm the director of the Yale Cancer Center and the president of Smilo Cancer Hospital. And I still see patients.

SPEAKER_04 2:50

And of course, he didn't say that he's the former president of ASCO and so many other things, but we'll let it slide for now and we'll talk about something provocative. So you and I were at ABC8 in Lisbon last year, where you presented a session with a very interesting title. I want to talk to you about it. So can we talk about cure?

SPEAKER_01 3:20

So where do you want to start?

SPEAKER_04 3:22

Well, first we'll start with the way you started your session, with the view of metastatic breast cancer. There's a river that has two banks. One bank, stages one through three, where they are most likely cured and will be treated with curative intent. And then there is the other side of the bank, stage four, no way to cross, cure is unattainable. But there might be a bridge somewhere inside. So let's talk about that bridge.

SPEAKER_01 3:56

Yeah, so um, of course, it would be wrong to say that every patient who has metastatic breast cancer has the potential in 2026 to achieve a cure, meaning the cancer is all gone away and the patient lives hopefully for many years and ultimately passes from something else. In my own mind, what's different from metastatic breast cancer than diabetes, for example, or high blood pressure, also chronic diseases, is that the vast majority, unfortunately, of women and occasionally men with metastatic breast cancer will ultimately lose their lives to breast cancer. And that's a reality that I think most of the people I take care of are well aware of. But the question is: to what extent are our treatments changing enough that for some number of patients, we should begin to poke the beer. We should begin to ask whether there's a subset of patients where we can somewhat deliberately try to go after that cure. And that's what the talk was really about. And I don't think it's by any means everyone. I think at the moment it probably is in a pretty narrow group of people. But I think the importance of that is that it speaks to what may be coming in the future. Because we have seen just phenomenal drug development over the course of the past, oh, I'd say 10 to 15 years. And the available treatments are just so different than they were.

SPEAKER_04 6:10

You opened that up for discussion.

SPEAKER_01 6:13

So let's talk about patients that whether maybe that's a possibility or where we're beginning to conduct clinical trials. I think it's really in two situations that overlap where we're all most enthusiastic. And the first is the setting of HER2-positive breast cancer, where we know that from clinical trials that have been conducted, that there's a small proportion of patients with fairly standard approaches who achieve long-term freedom from cancer progression. And some of those people are probably cured. I think we've done that already. So, first we're talking about HER2-positive breast cancer. And second, we're really talking about patients who are newly diagnosed with metastatic disease. Because if one has already received treatment, and in spite of that treatment, there has been a recurrence of cancer, it's that much less likely that we're going to be able to push the envelope as far as to the point that we can use terms like cure. And the reason for that, I think, should be obvious to most of the people who listen to this, is that if unfortunately, if cancer has come back in spite of treatment, it says something about the cancer. It didn't respond adequately to the first treatment. Doesn't mean that somebody can't go on and live a long, long time. And I have many patients, and I can think of one in particular, who initially presented with stage three HER2-positive breast cancer, now 20 years or so ago, had a recurrence, had received initial therapy with chemotherapy and antibody therapy and surgery and radiation, and had a recurrence just two years later or less. And that was now, I don't know, 16, 18 years ago. And she is still very much alive, working full-time, leading her life with cancer, but living a very long time and a very good life, I might add.

SPEAKER_04 8:35

Right. So let's talk specifics though. Let's mention some clinical trials. At the presentation, you mentioned three trials. So maybe we should just quickly go over those. The Cleopatra, the Patina trial, and DBO9. So maybe just quickly for our listeners to tell them what those trials were.

SPEAKER_01 8:55

So these were trials that weren't trying to achieve cure, of course, but are some of the building blocks that we've used. So Cleopatra was a trial done now a long time ago, asked a very simple question. And the question was: if you give a taxane and trastusimab or receptin, as is commonly known, would that treatment be better if you add perjetta or pertusimab? So is THP better than TH? Sure enough, it was better. It led to better control of cancer. And now, years later, an improvement in overall survival. But the important point is that there was a subpopulation of women on both arms, but much more so on the THP arm. So the group of women who received both receptin and projetive and chemotherapy upfront. There was a group of women who seemed through roughly 10 years of follow-up not to have any worsening of their cancer. And some of those people didn't have any evidence of cancer. If I remember correctly, it was in the low 20% range of people whose cancer was still a term we don't use very often when we talk about breast cancer, but I'll use it here in remission. And by that I mean either the cancer was gone or it was in such a state that it wasn't changing. And so that was the first clue that, you know, maybe there's a subpopulation of patients who just do really, really well. And my hunch, although I don't know this for a fact, is that many of those patients were patients who had de novo metastatic breast cancer, meaning they presented initially with stage four disease. So that's trial one. Trial two, patina, a trial that I was actually involved in. And that was a trial in women who had estrogen receptor positive and HER2-positive breast cancer. Received an initial course of therapy with a taxane and antibodies. And then after the chemotherapy was done, they received either the continuation of the antibodies and endocrinal hormonal therapy. So essentially an aromatase inhibitor or something like that. I can't actually remember if it was just an aromatase inhibitor or not, but half of the women received just hormonal therapy, half of the women received that plus the CDK-4-6 inhibitor, palbocyclib. And I will tell you, all of us assumed that this was going to be a negative trial.

SPEAKER_04 11:56

Let's pause here for a second because the Petina trial is actually worth unpacking. It was designed to ask whether adding a CDK-4-6 inhibitor, palbocyclib, to maintenance antibody therapy could improve outcomes in ER-positive, HER2-positive metastatic disease. Most investigators had written it off after the negative poloma results in a similar setting. What made patina different and what made the positive results so striking was the patient population and the sequencing. Chemoinduction first, then maintenance. The fact that it took so long to reach the required number of events is itself the story. People just did too well on both arms.

SPEAKER_01 12:44

Not in the beginning. We, of course, designed it with the idea there would be a positive trial. But then the results of the Edgeman trials with Palbocyclib came through and they weren't very encouraging. The follow-up was taking a long, long time. And we just assumed that it wasn't going to show anything. Well, the reason it took so long is because people actually on both arms did so well. So we didn't get to the necessary number of events, meaning recurrences, to analyze the data. But sure enough, women who received the CDK-46 inhibitor had a substantially longer time until there was any worsening of cancer. It was a dramatic difference. And then this past year at San Antonio, Otto Metzger, who was the first author, presented an abstract suggesting that not only did the palvocyclib prevent recurrences of cancer elsewhere in the body, it also seemed to have an impact on brain metastases.

SPEAKER_02 13:49

Wow.

SPEAKER_01 13:50

A finding that I think surprised some people. So that's trial two. And trial three is DBO9. I must confess that all those DB studies get me very confused. Oh, I know. It's Destiny 1, 2, 3, 4, 5, 6, and like I wish we could just change the name. But DBO9 is the trial that was done in the setting of women with metastatic breast cancer. And compared getting THP versus getting trestozimab directin, commonly called NHERTIO plus pretzimab. And sure enough, the group of women who received NHERTIO and Pertuzimab had a substantially longer time until the cancer progressed again. Now, I do have a caveat here, and that is that I don't believe that all women with HER2-positive metastatic breast cancer in the first line should be treated with NHER2 and PRTZimab. And the reason I don't believe that is twofold. One, it has way more side effects than getting THP. And for some people, they're really difficult side effects. And the second is that there has been no difference in survival scene yet. And it is, in my mind, very likely that if you compare getting THP followed by NHER2 and Pertuzimab versus the other way around, that there will be no difference in long-term outcome. I don't think it matters which drug you give first and which drug you give second in terms of the long-term outcome. So I think for many patients, the right initial treatment is still probably not in HER2. Although, of course, you can imagine there are some clinicians who feel differently. And if you were the maker of NHER2, you would feel differently too.

SPEAKER_04 16:04

I'm sure. But I'm so glad you said that. I am so glad you said that because this was the question that I've had ever since the results of DBO9 came out. First, they were comparing the results of a trial where the first one, the Cleopatra Protocol, had this six-month induction period or six-treatment induction periods, which was completely arbitrary. I guess there was a reason why they chose that, but it was an arbitrary number of treatments.

SPEAKER_01 16:40

And the chemotherapy was stopped and antibiotics were continued. Whereas with me and her two, it was continued somewhat indefinitely.

SPEAKER_04 16:47

Had you compared the two trials where the induction period was longer, the results may have been very different. It could be hold on. Because this comparison deserves a closer look. Cleopatra used the fixed chemotherapy induction of roughly six cycles before dropping chemo and continuing antibodies. DBO9, the Destiny Breast O9 trial, tested in HER2 plus frituzumap as a continuous regimen with no planned chemo stop. That design difference makes a head-to-head read nearly impossible. A longer induction in Cleopatra may have cleared more disease before maintenance, meaning the survival curves we're comparing aren't built on the same foundation. It's one of the reasons Dr. Weiner is cautious about rushing to making HER2 the universal first line standard. So you mentioned HER2 in the beginning when I had my first primary cancer in 2004. My doctor told me, no, not a good subtype to have. But now it seems that the HER2 is the one that we may be the closest to curing some patients. So why is that?

SPEAKER_01 18:06

That's true. I think it's because HER2 breast cancer isn't one disease only. HER2 positive ER-negative breast cancer tends to be different from ER-positive, although some of those ER-positive cancers are also very, very HER2-driven. And the reason it's different is when HER2 is a very strong driver, it's almost as if nothing else matters. So the cancer doesn't have a chance to mutate and evolve because HER2 is just shutting everything down. Or anti-HER2 therapies are shutting everything down. My friend and colleague, George Sledge, would often talk about smart cancers and stupid cancers. So the smart cancers are the ones that know how to mutate and know how to get around treatments and actually hurt patients. And the stupid cancers are the ones that are really much simpler because it's in some cases just HER2 that's driving their growth. And so you cut them off at the pass and you use an anti-HER2 antibody, and it has a profound effect. Not all HER2 positive cancers are alike. We've set this arbitrary cutoff, somewhat arbitrary. I mean, there were reasons for it, but I'm not sure it's the right cutoff of a fish of 2.0. And we have all of these patients, mostly who have ER-positive breast cancer, who have fish results that are 2.1, 2.2, 2.5, without strong staining for HER2, where we're really beginning to question how much anti-HER2 therapy matters there. But for others, it's just such a huge treatment. And it's such a profound treatment that for patients who have stage one, two, three HER2-positive breast cancer, the fact is that most of us have to scratch our head to come up with someone who had that situation, got appropriate treatment, and had a recurrence. We all have a few, but not many.

SPEAKER_04 20:25

And those that probably recur in that group are triple positive population who have estrogen receptor as well.

SPEAKER_01 20:33

It's actually both. Overall, the ER, the patients with the ER positive disease actually might do a little bit better because they also benefit from hormonal therapy. But I think it's really, now we're talking about Eric Winer Hunch, but I think it's two groups of women and occasionally men, two groups of individuals with breast cancer who will occasionally have recurrences. And one are the patients who really don't have disease that is HER2 driven, where in fact the anti-HERCU antibodies are just not doing anything. And the other are ones where even though they're highly HER2-driven, there's there must be something else going on. And that's a small number.

SPEAKER_04 21:20

Right, right. So we've been talking about the HER2 positive cancers, but why do you feel less optimistic about the other two types?

SPEAKER_01 21:32

I don't feel less optimistic. I feel quite optimistic. Good. So let's start with ER-positive breast cancer. ER positive breast cancer is not one single disease. It is a number of different diseases, and it's certainly at least two very separate entities sort of slower growing ER positive breast cancer that is sensitive to hormonal therapy and much more rapidly growing cancer where chemo. Therapy still plays a role, and the cancers are at much higher risk to recur. And those are sometimes called luminal A and luminal B based on results of old profiling studies or what's called intrinsic subtype among clinicians and scientists. You can also think of this to put it in terms that many women may understand better: tumors that have a lowish onchetype score versus those that have very high scores. I don't quite know where that cutoff is. But so ER positive disease is more than one disease. But the fundamental biology of ER-positive breast cancer is a little different. When it presents as metastatic disease, eradicating it becomes pretty difficult unless it is perhaps also virtue positive. And it just tends to be a little bit more like treating a different kind of malignancy, which is low-grade lymphomas, where people do well for years and years and years, but we don't have a way as commonly of totally eliminating the cancer, or at least we didn't in the past. The treatment of lymphoma, of course, has evolved dramatically as well.

SPEAKER_04 23:25

And of course, lymphoma is not one disease either.

SPEAKER_01 23:27

Lymphoma is totally not one disease. Lymphoma is like 30 diseases. But breast cancer is probably 30 diseases. We just haven't fully defined it. So what I'm more hopeful about for patients with stage four ER positive breast cancer is that chronic disease analogy will really become more and more true in that we will be able to manage patients. And, you know, look, eventually I think we'll cure everyone. But until we do, I think there will be a time when we are able to manage people for decades with hormonal therapies or hormonal therapies plus targeted therapies with hopefully minimal symptoms. And so living with metastatic ER positive breast cancer will be something people do, but it won't be such a difficult thing to do. And it can go on and on and on. Tribal negative disease is clearly our biggest challenge. Again, not one disease, sometimes exquisitely sensitive to chemotherapy, sometimes not. And we still have fewer tools. Immunotherapy contributes in many women, but not all. And its benefits are not nearly as great as the benefits of anti-HER2 therapy and HER2-positive breast cancer. And our drugs are just simply not as robust. So I think we will be there.

SPEAKER_04 25:42

Well, I hope so. It sounds a little better, but let's talk a little bit about cancer biology. And it's not one of the questions I had, but I'm really very interested in uh the studies of dormancy. And we started talking about ER-positive cancers. And one of the things that happens quite often with people, they have late recurrences. Many years later, all of a sudden, cancer just pops up. I heard somebody, and I can't remember now who it was, said that we will never cure cancer until we start curing metastasis, until we start attacking metastasis specifically.

SPEAKER_01 26:20

Dormancy is the concept that a cancer just stays quiet, is almost hibernating for years and years and years. And in truth, I can think of no other way of explaining what a cancer is doing when it recurs 25 years later. Because that happens with ER-positive breast cancer. There were women who 25 years later have a recurrence of that initial cancer. The question is always, where was Waldo for all those years? Yes. I don't think we have a clear answer, but very clearly Waldo had to be hibernating or dormant. And so the question is whether there is any way of figuring out which patients really do have dormant disease. Maybe everybody does, and it's a matter of preventing it from being reactivated, not eradicating those dormant cells. But either which patients have dormancy and how to get rid of those cells, or how to figure out when they're going to be reactivated and intervene at some point in time there.

SPEAKER_04 27:35

And why?

SPEAKER_01 27:37

Why does it no explanation? It does not appear from everything that I know to be related to something that everyone's always worried about, which is psychological trauma or stress. It is not necessarily related to another concurrent illness. We just don't know. And maybe it's just random. It's very, very difficult to know. But I think this raises another point, which is that when we treat cancer, there are really three very important variables. One is the cancer itself. And to some extent, we've been successful in targeting treatments to the cancer itself with many of the genomic studies that have been done. This is more true in lung cancer than in any place else. So there's the cancer itself. Then there's the tumor microenvironment for all the surrounding cells. And that's where immunotherapy works. And then the last very important point is the person. And I think we know much less about that. And when we think about studies that are looking at interventions with diet and exercise, we're really talking about how we can modify the host or the person in some way and other aspects of the host that are sort of unrelated to the cancer to get the cancer to behave better.

SPEAKER_04 29:23

Yeah, it's good that you mentioned that because, and you know how when people are first diagnosed, there's always this question. The first one, of course, is how long do I have? And I heard your presentation at San Antonio, I think, a couple of years ago when you were talking to your peers about how to answer that question. And I loved that. And maybe at some point, if you're willing, I would love to have you come back and talk about that. But the second question is always do I change my diet? What do I do?

SPEAKER_01 29:57

Do I Do I diet? Do I do I change my diet?

SPEAKER_04 30:02

Cut out all sugar because sugar feeds cancer.

SPEAKER_01 30:05

Yeah. So my answer to that is there's a reason why we have defined healthful diets as being diets that have fruits and vegetables and grains and somewhat limited amounts of dairy and somewhat limited amounts of animal protein. So I think the old food pyramid, not the new food pyramid that's been recently recreated, but the old one is a pretty good way to feed yourself. And short of participating in a controlled study in which there's a dietary intervention, I tend not to tell people to do anything very dramatic with their diet. I tell people that if they occasionally want to have some ice cream or more than occasionally have some ice cream, that that's probably okay. You know, the one concern we have, particularly for people with early stage cancer, is that there is some evidence that women who gain significant amounts of weight after breast cancer have a worse outcome. We don't know absolutely that it causes the worse outcome, but there's a reason to try not to gain a lot of weight. And of course, we have studies that have been going on looking to see if a woman who is overweight loses weight and exercises, whether that improves the outcome. But we don't know yet. There is, of course, though, this very interesting study that was conducted in Australia and Canada in colon cancer patients that was presented at ASCO this past year. I think it should have been an ASCO plenary session, but it wasn't. It was this fascinating study looking at an exercise intervention in people with early stage colon cancer, which demonstrated that there were dramatic improvements in outcome with a structured exercise intervention.

SPEAKER_04 32:08

And Dr. Neil Eingar, right, has done some work in that space as well here in the U.S.

SPEAKER_01 32:14

Neil, who used to be in New York and is now in Emory.

SPEAKER_04 32:18

Huge loss for us at MSK.

SPEAKER_01 32:21

Neil has done work in there. Um Jennifer Ligabel, who's up in Boston, has done a lot of work in this area. Katie Schmitz, who's at Pittsburgh, has done work in this area. Melinda Irwin, one of my colleagues at Yale, has focused on this. And it's a really important area. And when people started looking at this 30 years ago, I have to say that there are many people who are just so skeptical. Not only now do we believe that particularly exercise can improve people's quality of life, but it might have an impact on the behavior of the cancer.

SPEAKER_04 33:00

Wow, that's really incredible. Let's take a moment here. Because Dr. Weiner just touched on something that has quietly become one of the most exciting areas in oncology research, and one that directly affects every one of us listening. For years, the idea that exercise could influence cancer outcomes was met with polite skepticism. That's changing fast. The trial Dr. Weiner referenced, presented at ESCO 2024, was the challenge trial conducted across Australia and Canada in patients with early stage colon cancer. It showed that a structured supervised aerobic exercise program significantly improved disease-free survival, not quality of life, survival. That's a landmark result. In breast cancer specifically, the work has been building for over a decade. Jennifer Ligebell at Dana Farber has led studies examining whether exercise interventions can reduce recurrence risk in early-stage breast cancer patients. Katie Schmitz, now at the University of Pittsburgh, has been instrumental in establishing that exercise is not just safe during treatment, it's beneficial in improving fatigue, strength, and tolerability of chemotherapy. And Melinda Irvine at Yale, Dr. Weiner's own colleague, has focused specifically on the metabolic and hormonal pathways through which exercise may actually slow tumor growth. The current thinking is that exercise works on multiple levels, reducing inflammation, lowering circulating estrogen and insulin, improving immune function, and potentially altering the tumor microenvironment itself. It's not a replacement for treatment, but it may be one of the most underused tools we have. The bottom line: if you can move, move. And talk to your care team about what a structured exercise program might look like for you specifically. I want to ask you just a few more questions. And the question that is also quite important, and you touched upon it at your presentation, the oligometastatic. We've talked about it. And there are curative approach trials for the metastatic cancer that specifically mention oligometastatic. So how do you feel about actually? Is this a different type? Is it the same thing? Is the biology the same? How do you feel about oligometastatic?

SPEAKER_01 35:39

Let me say that in our trial in the translational breast cancer research consortium called SAFO, that's being led by Nancy Lynn and Heather Parsons, that we didn't want to allow local treatment of oligometastatic disease as a way of keeping peace. We decided that people could do whatever they wanted. There is yet to be a prospective trial that has demonstrated in breast cancer patients that treating a metastatic lesion locally makes a difference. And the one phase two trial that was done didn't show any difference. That hasn't stopped people from pursuing this. If a woman has one or two bone metastases or small lesion in her liver, it on some level makes some sense that if you treat that locally, that person could do better. I'm not convinced that's true. And while I respect other people's opinions, I would say prove it. And let's design studies that really can look at this question. The studies to date have not been positive. Outside of studies, we should be very careful in what we do because all of this treatment is not totally benign. And if oligometastatic disease is different, and by the way, oligometastatic disease is sort of in the eyes of the beholder. It's defined in many different ways in different studies. But if it's different, maybe it's different because the biology is different. So it's not that you need to go after those lesions. It's just that it speaks to a type of cancer that doesn't metastasize so widely, is fundamentally a little different. And that, yes, it's true that there are a limited number of sites of disease, but that's because it's a different beast, not that you have to treat those areas. So for the moment, I'm not going to weigh in and say people should or shouldn't do anything in their own individual practices. But I would say that there's reason to be cautious and there's reason not to jump into a mindset or to adopt a mindset that says that every time one suspects there could be just oligometastatic disease, that that should totally change our treatment approach.

SPEAKER_04 38:20

Right. But how do you feel about surgery in the metastatic setting? That's another question that comes up. And I think also you mentioned it. I guess right now it's still the case that if you are diagnosed de novo, you will not have any surgery on your primary tumor. How do you feel about that?

SPEAKER_01 38:42

So, in general, the studies that have been done, and there have been a number of studies that have looked at this, I think that the weight of the evidence is that resecting the primary tumor in the setting of metastatic breast cancer does not affect long-term outcome. I think that if a woman has cancer that is well controlled at other places and she has worsening of the cancer in her breast and it's causing problems, then I think it's totally reasonable to do surgery. And, you know, there are some patients who just don't want the constant reminder of feeling a lump in the breast on a daily basis. But there I would say if you're going to do surgery, I would aim to do less rather than more if that is possible. Finally, of course, there are patients who unfortunately have very large tumors that have caused local problems. And sometimes it's necessary to treat those. Of course, if that local problem is an ulcer or something like that, that's a contraindication to doing surgery generally. And sometimes radiation can be considered as well. It's really a case-by-case issue.

SPEAKER_04 40:02

And I guess there are more and more doctors who fall in that category where they say yes, case by case.

SPEAKER_01 40:08

And I just want to correct something I said. You know, for a long time it was thought that, for example, having a mass that had formed an ulcer, and this is not a common problem, of course, but that that was a contraindication to surgery. I think that comes, and I we'd have to have a surgeon here to either support me or refute what I'm saying. I think that comes from a day when people thought that you could do a mastectomy at that point with curative intent. And if the cancer had advanced that far, then the patient was generally not going to be cured. Therefore, you shouldn't do the surgery. I don't know that in somebody with metastatic disease who has a local problem like an ulcer, that surgery is contraindicated to deal with that local problem. And that's something we'd have to ask a surgeon.

SPEAKER_04 41:02

Thank you. Okay, this is the last topic that we'll cover. So you mentioned, right, the fact that now talking about cure is no longer taboo. And what does that mean actually for us? As you said, there are two things. There may be people, and I loved what you said, and I really would like you to talk about this a little bit. You said there are some people, and you mentioned it earlier, that there are some people on the Cleopatra trial, after eight years, they still hear, they're still on their first line of treatment, doing well. So you mentioned a term curative hope, and I loved hearing that because this was such a bomb for me to hear that there are some people on standard treatments are doing well. So how do you actually talk about curative hope with your patients? And do you bring it up at all when you talk to your patients?

SPEAKER_01 42:03

Patients often ask about this. I think, you know, it's always hard to remember whether you created a phrase or not. I think I created that phrase.

SPEAKER_04 42:12

I'll attribute it to you no matter what.

SPEAKER_01 42:15

Yeah. What it means for me is that we're not taking special steps. We're not suddenly coloring outside of the lines and doing all sorts of different treatments outside of a trial to achieve cure. But that there are some patients, and we recognize it, that with standard therapy, you can be hopeful that the cancer is going to not progress after many, many years. And in some people without any evidence of cancer. People bring this up. And again, outside of a trial, I wouldn't take a different approach than what I would with anyone else. Um, but I think that for the woman who presents with stage four HER2-positive breast cancer, that we know that if we treat her with a standard regimen, whether that's THP in the present or the future, with in a HER2-based regimen, I think we know that this is going to be a proportion of those women who are going to do extraordinarily well long term and many years later aren't going to have any evidence of cancer.

SPEAKER_04 43:26

Do you talk to your patients about that, especially those who come to you for the first time? Do you mention that possibility?

SPEAKER_00 43:36

Yeah, it usually comes up. I mean, these are the things that you talk about with people.

SPEAKER_04 43:41

Yeah. Okay, well, great. So last question. I promise you, it's my last question. So one thing is okay, people may be cured by using a standard kicker. But if not, there may be some curative approaches that we can use. And you mentioned the SAFO trial and uh Nancy Lynn was here and talked about it a little bit. And there is another trial called Horizon that my own oncologist at MSK starting specifically this new approach to sequential therapy trials like Sappho, like Horizon, where does the thinking come from that this would be a good curative approach?

SPEAKER_01 44:26

It comes from the fact that these drugs work after one another. So even when one drug stops working, the other works. So if you somewhat rapidly cycle them, that in theory you might be able to increase the proportion of patients where you eliminate all resistant disease. So we'll see how it goes. The proof will be in the future.

SPEAKER_04 44:57

Let's take a pause on these two trials, Sappho and Horizon Breast, because together they represent a genuinely new philosophy in treating HER2-positive metastatic disease. Most metastatic treatment has always been reactive. Use a drug until it stops working, then move to the next one. Both of these trials flip that script. Sappho, led by Nancy Lynn and Heather Parsons, sequences four lines of active HER2-directed therapy in a fixed pre-planned order before resistance has a chance to develop. Patients start with a taxane plus trestuzimap and retuzumap, followed by an HER2, then to cut NIP, Plastidium 1, and finally trestozomap and pertusumap and to cutnip. Each step hits HER2 through a different mechanism, monoclonal antibodies, antibody drug conjugates, and tyrosine kinase inhibitor, layering pressure on the cancer from multiple angles. And crucially, the goal is to intensify therapy for a defined period and then stop. Not manage indefinitely. Stop. Horizon breast takes a related but distinct approach. It uses the same class of drugs, taxanes, trastuzuma, pretuzema, in HER2, TDM-1 to cotinib, but personalizes the sequence in real time based on how each patient's cancer is actually responding. It uses CT DNA, circulating tumor DNA found in the bloodstream, alongside standard imaging to guide treatment decisions. Think of it as a dynamic roadmap. If the cancer is responding, the protocol adapts. If CT DNA signals a residual disease, the next drug in the sequence is deployed. Horizon Breast is a memorial slow catering trial, now open for enrollment, and its principal investigator, Dr. Pajram Razavi, will be joining us on the podcast very soon. Both trials are built on the same core conviction that for HER2 positive metastatic breast cancer, cure may not be out of reach, but getting there will require hitting hard, hitting smart, and knowing when to stop. Alright. So as the parting thought, when do you think we'll see cure? How does it look 10, 15 years from now?

SPEAKER_01 47:30

I don't think there's going to be anything that happens all at once in any group of patients. I think there are going to be people who maybe first with HER2-positive disease, we develop better regimens which are specifically designed to achieve a cure. I think in other subsets of breast cancer and other groups of women that we're going to have an increasing number of drugs that will keep the cancer really well at bay for a long time. And I just don't think it's going to be anything close to a one-size-fits-all approach. And I think we'll have that much more information in the next three to seven years. But again, my caution is outside of a clinical trial, there are times when one has to practice what I call creative oncology. But most of the time, you don't want to be doing that. And most of the time, it is important for people to recognize that we should be practicing according to what we've learned from clinical trials and good clinical practice. I've never really liked the idea or liked the comment when people say the best care is on a clinical trial. Well, if we knew for sure that that were the best care, then it wouldn't be a clinical trial, it would be standard care. However, what I would say is that some of the best doctors around the country are doctors who also design clinical trials. A clinical trial is not something that is thought up in some drug-induced bad dream that someone has. Clinical trials are carefully vetted and thought through, and groups of investigators discuss them, and they are reviewed by scientific review committees and institutional review boards. And finally, I'll just say that no sane person does a clinical trial to make patients do worse. So the hope is always that in one way or another, you're going to make people do better. So I do think that participating in clinical trials is really, really important. Part of the reason we know so much more about breast cancer than almost any other disease is because so many people have lined up to go on clinical trials.

SPEAKER_04 50:02

Thank you so much. Thank you so much for being here. This was wonderful. And I hope you'll come back. I promise not to pester you too much, but I would love for you to come back.

SPEAKER_00 50:17

My pleasure.

SPEAKER_04 50:19

Thank you so much. Take care. Bye-bye. Can we cure metastatic breast cancer? Dr. Weiner walked us through the landmark clinical trials Cleopatra, Patina, and DBO9 that are reshaping how we think about HER2-positive disease, and introduced the concept of curative hope. The idea that for some patients on standard therapy, long-term remission is not just possible, it's already happening. He also addressed ER-positive and triple-negative breast cancer, cancer dormancy, the role of exercise and diet, oligometastatic disease, and the promising new curative-intense trial designs like Sappho and Horizon. Throughout, he offered a clear and deeply human perspective, grounded in decades of caring for patients and pushing the science forward. If this conversation moved you, informed you, or gave you hope, please share it with someone who needs to hear it. And if you haven't already, subscribe to Life From Stage 4 wherever you listen to podcasts, so you never miss an episode. We'd also love to hear from you. Leave us a review, visit our website, and follow us on social media to stay connected with the latest in metastatic breast cancer research in our community. A reminder that the information shared in this episode is for educational purposes only and does not constitute medical advice. Always consult your own healthcare team about your individual treatment options and decisions. Until next time, keep living, keep hoping, and know that you are never alone.