The Changing Treatment Paradigm of HER2+ Metastatic Breast Cancer - Episode 10
Shared insight on the potential role for surgery in the setting of HER2+ metastatic breast cancer in the context of pharmacologic therapy.
Vijayakrishna Gadi, MD, PhD: Michelle, you touched on this a little while ago, but I want to unwrap this concept just a bit more, which is for patients who present with large breast masses and maybe have oligometastatic disease, what is the role of going back and trying to completely rid any sites of disease in these women? And how aggressive should we be?
Michelle Melisko, MD: As I mentioned, the standard thinking, at least in my institution with the surgeons based on the randomized clinical trial data, is that there is no survival benefit from surgery in a patient who has de novo metastatic disease. And even when they looked at different subsets in various trials, the only group that seemed to benefit was the ER [estrogen receptor]-positive, HER2-negative with a single or isolated bone metastasis. But that has not been my experience. We have sort of broken the rules many times, largely based on patient preference, as I said, these women had a large breast mass. Oftentimes it will shrink away in the neoadjuvant setting. We do, as Dr Geyer said earlier, we treat these sort of aggressively, these oligometastatic patients, trying to treat them with curative intent, giving them a CLEOPATRA-like regimen. Sometimes I will even add the carboplatin in as if it were a true neoadjuvant patient and get a really good response. And then you have no metabolically active disease anywhere, and typically our pattern is we take them off the chemotherapy, keep them on dual HER2-targeted therapy. Or in the case of someone who has triple-positive disease, we might add hormone therapy, an aromatase inhibitor [AI] if they’re postmenopausal, OS plus AI plus Herceptin and Perjeta [HP] if they’re premenopausal, and then wait 4 to 6 months and make sure that everything stays stable.
That’s what our surgeons have demanded in terms of wanting the patient to demonstrate that their disease is going to be quiet everywhere else in the body before taking them to surgery. But there’s always this discussion about, do you go for broke, and do you do a lumpectomy plus sentinel node plus/minus full axillary node dissection? Because these women almost always present with clinically node-positive disease, which under the current standard—although that’s changing—would mandate a full axillary node dissection. And then if they have a lumpectomy, do you follow up with radiation, and what’s the radiation field? And then the whole surgical and radiation oncology role of de-escalation, there are a lot of moving parts, and I think that we don’t really have the answer. But I’m curious to hear what my colleagues, what their institutional practices are, because I feel that in the community, I think they’re fearful. They generally will do more than less, and that’s because patients want more, they want that breast mass gone, or even if the breast mass is gone from chemotherapy, they’re constantly feeling their breast wondering, “Do I feel this? Do I feel that?” And I think that having gotten breast-directed therapy, whether it’s a lumpectomy and radiation, or in many cases, these women will want bilateral mastectomies, it gives them hope that they will be cured. I think it’s a psychological measure oftentimes, but it’s an important psychological measure.
Nancy Lin, MD: At our institution, not all de novo patients are the same, and so we are really thinking about them in different ways. There’s the patient who has potentially a locally advanced HER2-positive breast cancer and 1 or 2 discrete bone metastases on staging imaging. For those patients our terminology is “curative hope.” We treat them with curative hope, with essentially a curative intent regimen of neoadjuvant therapy, surgery, radiation as needed, and potentially radiation to the oligometastatic sites. That’s one group of patients. Then the other group of patients might present with quite significant liver disease, and they might have a T1 or T2 lesion in their breast. Those patients we generally don’t offer breast surgery, we treat them as we would treat somebody with metastatic breast cancer. The exception to that is occasionally those patients progress only in the breast, and that might be a situation if they’re doing well on HP maintenance that we might offer local therapy to the breast in the hopes that then we could just continue HP maintenance afterward if that’s the only site of progression. But I think we try hard at the beginning to classify patients because patients generally fall into 1 of 2 two categories, and for patients who we’re planning to treat with so-called curative hope, we tend to present those at our tumor board meetings so that there’s a consensus that that’s a reasonable patient to offer that aggressive therapy to.
Vijayakrishna Gadi, MD, PhD: Nancy, I love the term curative hope, and I’m definitely adopting that in our practice. I’ll say that the bulk of the data regarding these ideas of the old term of “toilet mastectomies” etc in patients who have metastatic disease are from places like Tata Memorial Hospital in India or Turkey. And if you look at the trial data, they did everything we would do, but the truth is that patients in this country have access to a lot of different tools and a lot of different expertise that is just not available to others. One still wonders if these things are still appropriate in the patients we’re seeing, at least in the United States. And I would argue that until we have definitive homegrown data, that we should still continue to explore these concepts. Chuck, I don’t know if you have a thought on that.
Charles Geyer, MD, FACP: For me, I always worry about the opportunity lost when you have this. We do adjuvant therapy because we believe it is getting rid of hidden occult metastatic disease. So we’re basically saying that, “If I can see it, then it’s no longer curable.” That’s just magical thinking to me. Clearly as we get increasing sensitivity and look harder, you might see the tumor sticking its head out of the foxhole, but to act like there’s a fundamentally biologic difference there, I’ve never understood that. The other thing to me looking back that we have to remember is, back in the day when our first modality beyond surgery was radiation therapy and we had horrible disease, we learned that it helps with local control, but it doesn’t have a systemic effect, so we didn’t do much radiation. Then a few radiation oncologists, once we were doing adjuvant therapy said, “Maybe we should go back and look at this, maybe it will do something.” Now in the setting of chemotherapy, local treatment, optimal local treatment, improves survival.
We see that, so now do we need a study in this situation, which would be virtually impossible to do? Or should we just be extending it and embracing it as a community? Lajos Pusztai, MD, DPhil, is interested in trying to come up with a study to address this. He’s done a beautiful job of reviewing the literature. The interesting thing is apparently our colleagues in Europe, in ESMO [European Society for Medical Oncology], have sort of taken the position statement that this is a group where we probably ought to do as Michelle is suggesting. So there’s already a sense that looking at a trial here, could you even do it in the HER2-positive space? Probably not, because of what we just heard. Because at my institution too,we treat those patients with curative hope. Once the equipoise goes, you can’t answer it. If you’re going to study it, maybe it’s luminal B patients, I don’t know, but HER2-positive, it’s a tough place to think about that, personally.
Nancy Lin, MD: It makes you wonder whether there is the will and the way to do a centralized registry. This is the sort of question that lends itself to a registry that any community-based oncologist or academic-based oncologist could essentially register their patients when they start treatment, so that it’s a fair denominator. And see what happens to patients over time, you’re not assigned treatment, but to understand. If we had data on 100 patients treated with curative hope where we could say, “X percent of patients are off treatment and disease free at 5 years,” that would be practice-changing data. And it wouldn’t require, I don’t think, a randomized trial to show that. I think with the last year and a half, or 2 years now, of COVID-19 expanding our minds in terms of thinking what is possible to do that doesn’t require study visits to an academic center? I think this is the sort of question that would be very well suited to that kind of effort.
Vijayakrishna Gadi, MD, PhD: I know SWOG [Cancer Research Network] was exploring exactly that Nancy, prepandemic, and I don’t know where that concept sits right now, but maybe we can revisit it.
Transcript edited for clarity.