HER2+ Early-Stage Breast Cancer

Adam Brufsky, MD, PhD: There’s a lot of cool stuff from ASCO [the American Society of Clinical Oncology Annual Meeting] that will weave into this, but let’s go to the pre-ASCO days. Let’s start with Carey. Someone comes in with HER2-positive disease. She’s got a core biopsy so she’s HER2 [human epidermal growth factor receptor 2] 3-plus copies. Maybe she has some estrogen receptor [ER] expression; maybe she doesn’t. How do you treat her when she comes in?

Carey K. Anders, MD: This is usually in concert with our surgeons, and the size of the primary tumor is one of the first things we’ll look at. If we already know the patient has node-positive disease, then we all feel very comfortable to move forward with neoadjuvant chemotherapy in HER2-directed therapy. But for the tumors that are less than 2 cm, particularly those that are ER-positive/HER2-positive, we’re very comfortable with the surgery-first approach to see if we can weave in de-escalation strategies for that patient.

Adam Brufsky, MD, PhD: Yes. The question is, what is your cutoff? Is it 1 cm? Is it 2 cm? That’s the first question raised. Someone comes in with, for example, a triple-positive disease, right? Let’s say it’s T1c triple positive. There’s enough out there that says some of these people are really not HER2 enriched, so maybe we’ll do surgery on them. What do you guys do at Duke Cancer Institute?

Carey K. Anders, MD: The original APT study allowed up to 3 cm, but if you look at the patient characteristics, only around 9% of those patients had a tumor between 2 and 3 cm. When they move forward with the ATEMPT trial, all the primaries were less than 2 cm. I really use that as my cutoff. I do, however, treat a tumor that’s your ER/PR [progesterone receptor]–positive HER2-positive, 1.8, 1.9 cm. I worry more about those if they’re ER/PR-negative HER2-positive than I do the ER-positive/HER2-positive. It’s not to say that I would transition that patient to neoadjuvant chemotherapy. I might consider a different chemotherapy backbone than just the 12 weeks of paclitaxel-trastuzumab. I might think about a HER TC [docetaxel, cyclophosphamide] regimen in that case and give a Taxotere-Cytoxan backbone to a patient who has a larger T1c ER-negative/HER2-positive, node-negative breast cancer.

Adam Brufsky, MD, PhD: Virginia, is that the same way you guys do it?

Virginia Kaklamani, MD: Very similar. We’ve been burned with tumors that have come in at 1.8 cm, but at the time of surgery they are 0.8 cm. Exposing that patient to a TCHP [docetaxel, cyclophosphamide, trastuzumab, carboplatin]–type regimen, I think, would really be a little too much. So, I use a 2-cm or node-positive cutoff. If they’re less and node-negative, I will do primary surgery and then decide on postadjuvant therapy. Otherwise, I will usually give them TCHP.

Adam Brufsky, MD, PhD: TCHP, all right. Rashmi, what are you guys doing there?

Rashmi K. Murthy, MD, MBE: Very similar approach. I use the 2-cm cutoff to decide if that patient goes to surgery first, and then I treat them in the adjuvant setting with, ideally, a de-escalation strategy. But if they have a tumor either 2 cm or greater or node-positive, then I generally opt for TCHP in the neoadjuvant setting.

Adam Brufsky, MD, PhD: What’s the smallest one you treat, Mark? Here’s a case: A woman comes to you for a second opinion. It has 2 mm and in a setting of a lot of HER2-positive DCIS [ductal breast carcinoma in situ]. A little bit of micro: It is at 2 mm that someone stains as HER2 3-plus copies and her nodes are negative. What do you do?

Mark D. Pegram, MD: I’m not impressed that those need-adjuvant HER2-targeted therapy at all. My cutoff is about 0.5 cm, anything like that. Especially if they’re steroid receptor positive, I’m very comfortable omitting HER2-targeted therapy altogether. I worry about the cases that are 0.4 cm, ER negative—a young patient perhaps. In those cases, you have to have a balanced discussion with the patient and tell them the pros and cons of each approach. They may have a strong preference one way or the other that can help make the decision at the end of the day.

Adam Brufsky, MD, PhD: Rashmi, everybody always quotes the University of Texas MD Anderson Cancer Center paper with a 13% recurrence risk in stage I disease as the reason to treat people like this. But I don’t think there are that many T1a and T1b in there, are there? Carey, are there a lot of that or not?

Carey K. Anders, MD: No, that’s my understanding, as well, that the large majority of patients—and Rashmi can chime in—were more in the T1b, T1c, so I would agree. I do not usually offer adjuvant HER2-directed therapy for a tumor that’s 5 mm or less.

Adam Brufsky, MD, PhD: Okay.

Virginia Kaklamani, MD: There was a retrospective study that was presented a few years ago at the San Antonio Breast Cancer Symposium from the Netherlands, which was pretty much a tumor registry, so it was absolutely not clinical trial material. But it was interesting because some of these patients who were T1a were treated with trastuzumab-based therapy, and some were not. Even in T1a, the benefit of trastuzumab was there. That’s why in the case that Mark presented—where it’s a young, 0.4-cm tumor, and ER-negative—I’d show them the graph. The graph is pretty nice, and then they get to decide.

Adam Brufsky, MD, PhD: I was thinking of that too. It’s tough. The whole point is we’re a little more nuanced than our surgical colleagues. We like to think about what we do a little, about the long-term adverse effects of what we’re going to do, and we just don’t jump as much as we used to. That was the theme of ASCO for this year, actually. I’m really on the fence here. I really am.

Mark D. Pegram, MD: The hardest thing for me are the large HER2-positive DCISs that have a little bit of microinvasion in almost every section. It’s very hard to guesstimate what the actual volume of disease is in those cases. I find those probably the most challenging.

Adam Brufsky, MD, PhD: The worst thing is, 60% to 70% of DCISs are HER2-positive, right? How do you know they’re not staining in DCIS and just making a mistake, that it’s not invasive, or not because you can’t see the base of the membrane? I don’t know what to say. It’s a real toughie.

Transcript Edited for Clarity