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HER2+ Early Breast Cancer Roundtable: Factors Guiding Treatment Before and After Surgery

This video highlights both disease- and patient-specific characteristics that may impact treatment options for the management of early breast cancer, including pre-surgery treatment outcomes, adverse events, chemotherapy de-escalation, and more. 

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

This video is sponsored by Phesgo.


Dr Maryam Lustberg: So we'll spend some time talking in more detail about pre-surgery considerations in HER2+ early stage breast cancer as well as some of the decision-making that comes into play after patients go to surgery and we have additional pathology data.

So, in discussing things with my colleagues, we've been talking about the clinical situation of my patient with lymph-node positive, hormone receptor-positive, HER2+ breast cancer. Maybe talk me through in terms of some of the pitfalls that maybe our colleagues watching may encounter in interpreting a pathology report.

I know that HER2 status has been shown to have some discordant results depending on which lab has processed the result. Have you had any experiences in terms of just the trickiness of HER2 testing and how do you manage that in your practice?

Dr Giancarlo Moscol: Well, I would say when we see new patients and they get the pathology outside, we recommend that we rerun the tests because indeed, there has been a lot of discrepancy. You can really kind of read in between the lines when you see, I don't know, I see a high grade high-Ki-67, but HER2 0 or 1+ or the opposite, right, like a HER2 3+ with a Ki-67 or 5%, 10%, Grade 1, Grade 2, sometimes things don’t add up. So I prefer to just rerun the receptors. We use monostoichiometry and we do reflex FISH for the two pluses. Of course, the counter side of that is that it takes a little extra, the FISH is between 5 to 7 days, but I tell them that it's better to make sure that we're getting all the information correct from the beginning because that's going to dramatically change the way how we treat them, right?

It's true also that now we need to account for what is considered tumor heterogeneity, right?  We know that it's not just about the individual cell but the behavior of the cells as a group and how that may impact future choices is yet to be determined. But I do believe that unfortunately we continue to use relatively all criteria. I mean the way how we measure HER2 unfortunately has not really kept up to date with the technologies we have now to target HER2 treatment. So in the future I kind of look forward to maybe having an artificial intelligence and some digital pathology solutions to standardize, right? Because I believe that there's so much discrepancy between some pathology labs and even within the same institution depending on... We always have this joke, if you talk to the pathologist Monday morning vs Friday afternoon, you may end up getting discrepancies there. So I believe that potentially computers may help us a little better there.

Dr William Gradishar: And I think that there are situations where, for instance, patients in both early- and late-stage disease. Let's start with the latter first. If you have somebody with metastatic disease, they progress, maybe the pattern of metastases or progression is different. You rebiopsy them and then suddenly you find that the patient is not the same HER2 status as before. It could potentially change how you approach the patient. But as was pointed out, there can be—the testing may be an issue, the testing, it may be tumor heterogeneity, or the age-old evolution of the tumor thing, which, so nobody knows for sure. The other situation that we encounter changes perhaps is the patients who get preoperative therapy, they go to surgery and at the time of surgery you check the specimen. Now all of a sudden there's no HER2 in it. What do you do with those patients? So I think that it can cause some confusion for practitioners about how they approach those situations.

Dr Maryam Lustberg: So, we have confirmation of this triple-positive node-positive breast cancer. I think we have previously discussed why it's important to do systemic neoadjuvant chemotherapy and have had a chemo backbone plus dual HER2-targeted therapy. My patient did struggle quite a bit during treatment. She was experiencing increased fatigue and also she was starting to have early neuropathy symptoms that were progressing with more numbness and tingling. And I think there were definitely points when she was presenting where she wasn't sure she wanted to keep doing this. So I think it really took some additional discussion to understand better how it was affecting her functionally. And I did end up dose reducing her chemo backbone because of the progressive neuropathy symptoms. So, just wanted to hear additional maybe challenges that you have faced with your patients supporting them through neoadjuvant chemotherapy and what modifications do you usually make if they're struggling.

Dr Giancarlo Moscol: So whenever a patient is starting taxanes we actually recommend cryotherapy. So we're doing icing. I explained to them the idea is that you're trying to limit the amount of taxanes that get to the fingertips and the toes. Many different ways to do that. So you can either get a bucket with ice and water submerge hands and feet and try to keep it before, during, and after the infusion of the taxane. We are seeing very good responses. We are preventing neuropathy. We're trying to prevent neurological damage.

As a matter of fact, you can actually get also a chemotherapy gloves and socks now online. And I also encourage them to do that because it's better to prevent than to treat neuropathic damage. Once that happens, we're talking at months, sometimes even years to recover. The cytopenias are tricky, right? With the carboplatin, especially in the neoadjuvant setting. That to me, I have better experience, sometimes I need to cut back and do the weekly rather than 2 or 3 weeks and be mindful offering supportive care. I always tell these patients that between the diarrhea and the fatigue, sometimes IV fluids to help them recheck magnesium levels and provide enough supportive care to help them keep at full dose will be recommended.

Dr Maryam Lustberg: You guys are early adapters with some of the cryocompression?

Dr Giancarlo Moscol: Yeah.

Dr Maryam Lustberg: So there's a definitely promising phase II data and there's now going to be a phase III SWOG study looking at cryocompression vs low-dose compression. So really good to hear that you guys are using it, and I tend to wait for more of the phase three III data, but it's interesting to hear different practices.

Dr Giancarlo Moscol: Yes, yes.

Dr Ting Bao: Yeah. Our institution does that too. At least the Manhattan site.

Dr William Gradishar: Yeah, we do too. That or bags of peas, whatever.

Dr Maryam Lustberg: Yes.

Dr Giancarlo Moscol: Carrots. You can eat them later.

All: Yes. Yes.

Dr Maryam Lustberg: Are there tricks that you do to support your patients?

Dr William Gradishar: I think we do a lot of the same things. I mean the emergence of neuropathy is one of the big issues. I don't know what... We try the usual things. We even send people for acupuncture—works sometimes, not all the time. We do the cryo, they're icing their head in many cases already so we're just expanding the icing to other appendages and in some cases it makes a difference. So anything that makes patients feel like they can get to the finish line is our goal.

Dr Maryam Lustberg: And so my patient did finish her preoperative regimen. She was able to get the surgery. she was a candidate for breast conservation therapy and she went—after surgery when we received her pathology data. Just to remind everyone she had strongly hormone receptor-positive breast cancer in addition to HER2+. So what would be your expectation in terms of pathologic response vs not for her based on her hormone receptor status?

Dr Giancarlo Moscol: So the trifina showed that patients that are ER+ positive have about 40% of of PCR vs ER- negative. It's a little higher, 70%. So that's what I discuss with patients. I tell them that it's not to be disappointed because we can always switch treatments and try to catch up on what has not been achieved. So it's not unheard of that you don't get to PCR when you're ER+ positive. The advantage is, of course, that you can go after the estrogen receptor later. So that will be a different take. And of course, I, again, focuse on the fact that we're not talking about a sprint, but rather a marathon. It's going to be a journey. So we need to make sure that we're pacing ourselves and our treatments and the strategies to support them.

Dr Maryam Lustberg: Just curious to hear, then, how are you supporting your patients in that post-op discussion when they have residual disease, and what do you tell them?

Dr William Gradishar: Well, I think that we would not say we're going to plan B, we're just continuing the treatment plan that we would've considered from the outset, which is that we modify the anti-HER2 approach. These are the kinds of patients that would get T-DM1 because they have residual disease. We're exploring, of course, other ways of perhaps enhancing that through clinical trials with the addition of tucatinib or even eventually probably other antibody-drug conjugates may supplant T-DM1 in that setting. We'll see. But the point being that patients who have their anti-HER2 therapy switched are going to do better than if you continue the same anti-HER2 therapy they started with. And of course, the anti-hormonal therapy is a critical element of their therapy overall.

Dr Maryam Lustberg: Yes. And you made the really important point earlier in terms of HER2 status at the time of the surgical specimen that has experienced anti-HER2. And I just want to reemphasize that important teaching point for the audience based on the Catherine data and analysis of biomarkers. So whether HER2 status is negative or positive, would you change your course?

Dr William Gradishar: No, we would continue anti-HER2 therapy in that setting. And even though the number of patients in that trial that led to the use of T-DM1 in the residual disease setting who had a switch from HER2+ to negative wasn't huge, those patients still benefited from T-DM1. So right now, the evidence would lead us to say you continue anti-HER2 therapy.

Dr Maryam Lustberg: Yeah. And I think it was causing such confusion in our institution where repeating those biomarkers, particularly the HER2 status, when it was not going to change clinical decision-making. We actually made a decision that if we were absolutely positive that it was HER2+ to begin with, we would not necessarily repeat in the surgical assessment because it was very easy for somebody to just say, well, oh, this is a HER2-negative- tumor.

Dr Giancarlo Moscol: I Agree. As a policy, we usually don't repeat biomarkers, we just go with the initial biopsy because we're trying to prevent things be more difficult to interpret later. Absolutely.

Dr Maryam Lustberg: And so I think it does feel like a marathon to many patients because especially if they have residual disease, obviously it's 14 additional cycles of every three week treatment. How are you supporting patients through these very long treatments?

Dr Giancarlo Moscol: I usually see them every other cycle at the beginning just to understand what type of toxicity they may be experiencing. It's a little challenging if they already had some neuropathy from the taxane because it can get a little worse while on treatment with T-DM1. I have also seen some liver alterations, which may or may not be related to also the diet that they have. So I usually try to tell them, try to stick on a low-fat diet and try to exercise some to the measure that you're able to do so. With that being said, I would say the majority of patients tend to recover probably after the first two cycles of T-DM1 could be more challenging because they're recovering from surgery, entering radiation, and then dealing with the residual toxicity and the new toxicity. You have to really try to support them at their best. After that it tends to get a little easier, but still some patients are not able to tolerate even after you reduce the dose.