HER2+ Early-Stage Breast Cancer Roundtable: Standard of Care and Alternative Options for Breast Cancer Management

This video highlights the current guideline recommendations for treating early breast cancer as well as the current guidelines for metastatic breast cancer. 

For more HER2+ early-stage breast cancer content, visit the Resource Center.

This video is sponsored by Phesgo.

Dr Maryam Lustberg: There have been many advances in the management of HER2+ metastatic breast cancer. We’ll spend some time discussing these emerging strategies that have been incredibly helpful in managing patients with HER2+ breast cancer and helping them live longer and better. So in just continuing our discussion about patients with HER2+ breast cancer that I know we’re all seeing in clinic, my patient, we’ve spent some time talking about early-stage management. We’ve also all been surprised when we sometimes order these staging studies on higher-risk patients and we do end up having evidence of distant spread. And so let’s spend some time talking about how our management decisions would’ve been different if, let’s say, we found a solitary lesion within the liver that showed up on abdominal CT imaging that was highly suspicious for a metastatic disease. And just to recap, this is the same patient that initially presented with a 2 cm breast mass with biopsy-proven lymph node involvement. That and her biomarkers suggested strongly hormone receptor-positive HER2 overexpressing breast cancer. We thought it was early stage, but now we actually have, unfortunately, evidence that she may have liver metastases. So I would love to hear your thoughts in terms of how the management could be different or would be different compared to an early-stage breast cancer situation.

Dr Ting Bao: So I would first do a liver lesion biopsy just to confirm and also confirm the receptor status, assuming is triple positive again and confirm metastatic breast cancer in the liver. Then I would really have a sit her down and her family have a detailed discussion. So now unfortunately, you have metastatic triple-positive breast cancer and what to do. At this point, I wouldn't recommend surgery. So we would go start with systemic treatment, chemo plus anti-HER2 agent, and I'll go into the detail of treatments and, yeah, answer her questions. I have quite a few patients with that. Some of them are really anxious. So just really try to explain this is really not a death sentence and metastatic HER2+ breast cancer prognosis is getting so much better after all this new anti-HER2 agents. So don't lose hope. Let's keep fighting.

Dr Giancarlo Moscol: I agree. The only thing, the other thing that I would also highlight is especially given the HER2 background, I would get an MRI of the brain to make sure we're not missing any hidden lesions there. But, unfortunately, when the moment you have advanced disease, I explain to them that we can still treat this and potentially aim to get into a complete response and put the patient into remission, but the role of surgery is still questionable, right? I mean, we don't have great evidence about doing surgery that's currently being studied. The net advantage of the HER2 positivity is that you can certainly tackle that down and since it's the main driver, I guess signal, in the disease proliferation you can get very deep responses. So it's not uncommon that we see that these patients, after they get 4 or 6 cycles of the so-called induction treatment they may get into complete responses. Right. I've seen that many times. And if we manage to get there, we can certainly buy many extra years of life.

Dr William Gradishar: Yeah. So I think one of the things that we've observed is that we're probably in the US at least seeing more patients presenting with de novo metastatic disease than recurrence of their prior HER2+ disease, which is largely a reflection of the effectiveness of our therapy. So when the patient didn't have metastatic disease, we could very legitimately say that a high fraction of those are going to be cured. This patient, as already pointed, out probably isn't going to be cured but could have many, many years ahead of her, which wouldn't have been the case before HER2-directed therapy. And as pointed out, you know, we don't typically recommend surgery for these patients. It's still individualized and debatable, but the clinical trials have failed to demonstrate that surgery, even in these kind of patients, is going to extend their survival in any way. But of course, we still have individual discussions about specific patients. And I just wanted to make one other comment about the chemotherapy. So we currently give chemo with dual HER2-targeting therapy. And if the patient has the expected good response that we would measure by the scans, then we often get rid of the chemotherapy and continue the anti-HER2 therapy, and that would be potentially indefinite. So in some of those patients, the consideration might be to, rather than giving sort of IV medications at that point, to consider a subcutaneous form of the anti-HER2 therapy.

Dr Maryam Lustberg: So one thing I wanted to get all of your opinions on is that we know that this landscape of HER2+ metastatic treatment paradigms continues to change. I think we're all aware of the Cleopatra regimen that really put taxane plus dual HER2-targeting, like we've talked about, with trastuzumab as pertuzumab, as clearly the first-line standard of care. In this study it was docetaxel that was the taxane backbone, but there are multiple centers and there is now real-world data about using kind of more weekly paclitaxel-based regimen as well. So one thing I wanted to ask about is, for patients who maybe are a little more frail, are you using more the weekly taxane regimen or what are you doing in your practice in that regard?

Dr Ting Bao: We use more weekly paclitaxel yes, yeah.

Dr Maryam Lustberg: It's better tolerated has been my experience but more time intensive because obviously they have to come in.

Dr Ting Bao: Yeah. Sometime when people are diagnosed with metastatic breast cancer, they want to come in more frequently at the beginning, that is. Yeah. So, that's well accepted.

Dr Maryam Lustberg: Are you using more weekly?

Dr Giancarlo Moscol: No, I still use docetaxel, and I actually wanted to gather your opinion about the number of cycles because it's between 6 and 8. In my experience, if the patient manages to get to 6, I just recommend going to 8, especially if you're going to get a deeper response. Most of the times, you know, it's the neuropathy and the cytopenias that limit the take, but, I don't know. Have you already switched to full paclitaxel or you continue to use docetaxel?

Dr Maryam Lustberg: I tend to use a mix. So, for example, generally I was following essentially the published Cleopatra regimen and I had seen the smaller study out of Memorial Sloan Kettering from a few years back talking about the weekly paclitaxel. And it still, I felt, well, I have a stronger study with Cleopatra, let me just use docetaxel. But then just recently there was actually a very large real-world data series that again reconfirmed that the weekly regimen has similar efficacy. So I'm using it more for my older patients who tend to be a little more frail, and I do want to keep a closer eye on them with the weekly. In terms of the number of regimens in my practice, I typically, the median number of cycles that was within the Cleopatra regimen was 6. And I think that's, I tend to do 6 unless they are having trouble, in which case I either dose reduce or stop a little earlier. Do you, what was your approach?

Dr William Gradishar: So we tend to still use docetaxel, and there's a variety of different things that account for that, including the fact that, you know, patients coming downtown to pay $60 to park in the parking lot every week is not appealing to many people. But that said, I would take into account how well the patient is in general good shape, can they tolerate docetaxel. If not, then I feel perfectly comfortable with weekly paclitaxel. And to your point about the response, if somebody had fairly significant disease and at 3 cycles they had a pretty dramatic response and at 6 cycles the imaging showed that they continue to have that great response, I might push another couple cycles. But many patients, you start out saying, we're going to give you about 6 cycles and the chemo's going to go away. They're sort of looking forward to the chemo going away.

Dr Maryam Lustberg: So I think, you know, obviously we're all aware that additional agents are being tested in terms of this first-line setting, but right now this is our solid standard of care. So I think, kind of building on what you're saying, just how long to continue the dual HER2-targeting therapy, I tend to continue until progression, or if they're having cardiac issues that necessitate stopping. There is going to be a prospective study specifically looking at giving the patients the choice of whether to stop dual HER2-targeting therapy or continue. And so, I think patients can have very strong preferences in terms of whether to continue or not, but I think it is a data-free zone right now in terms of, generally, I think most of us are continuing. Are you?

Dr William Gradishar: Yeah, I think it's, you know, the ultimate question comes back to you usually— “What would you do, doc?” Or “What if…,” you know, that's the inevitable question that we encounter. And even if there's a study, they're going to still be asking that question, and we don't know the answer. There are some patients who, you know, they're 2, 3, whatever number of years out. And they ask how long we going to be doing this? And there are other patients who say, “I never want to stop.” It's just like the patients who are getting anti-hormone therapy, why are we stopping?

Dr Maryam Lustberg: Right, right. And I think this is where I think having the option for some breaks in therapy, even if it's a short time, if they want to take a vacation, you know, I tend to be obviously flexible about that. And I think, kind of shortening the amount of time that patients are spending in the facility getting dual, HER2-targeted therapy, I think, when kind of subcutaneous formulations of trastuzumab and pertuzumab can shorten the wait time. And so for patients who have been on therapy for a long time that that can be in good time saver for them.

Dr Ting Bao: So if you, they're on anti-HER2 agent for years, do you do echo like every few months or every year?

Dr Maryam Lustberg: I tend to do it a little less frequently if they've been stable for a long time, anywhere from 6 to 12 months.

Dr Ting Bao: That's what our institution has changed to, yeah.

Dr Giancarlo Moscol: Yeah. We do 6 months too, yeah.