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DR GRADISHAR: This was a lady I saw about 6 or 8 weeks ago, a 48-year-old African-American woman who worked as a court reporter. She had no other significant history other than mild hypertension — no family history. She actually went to her gynecologist for a routine PAP pelvic exam, which was normal, but by the way, she was noted to have a large breast mass that was changing the contour of her left breast. There was sort of a bump there. No breakdown of the skin.

Additionally, she had some palpable nodes in the left axilla, all freely movable, none fixed, and the largest by exam was around 2 centimeters. The remainder of her exam was okay. She got a mammogram that confirmed a spiculated mass in the breast, corresponding to the physical findings, and the lymph nodes in the axilla could also be visualized on the mammogram, and the biggest one, using that measure, was about a centimeter and a half.

She had a core biopsy of the breast and the node. They were ER-negative, PR-negative, HER2-positive by FISH, and she got staging evaluation, CAT scan and bone scan, all of which were negative.

The issue is how you would approach this woman who at the outset is probably not a surgical candidate.

DR MORROW: And why is she not operable?

DR GRADISHAR: You could argue that, I suppose, as well, with the surgeon in the room. But she has multiple palpable nodes in her axilla, though none are fixed.

DR MORROW: I’m not necessarily arguing I would operate on this case, but she doesn’t, as you describe her, meet any of the classic criteria for inoperability/mandatory neoadjuvant therapy.

DR LOVE: What would you likely be thinking, if you saw her?

DR MORROW: What I would be thinking in this case is: It is true that in people who have multiple evident nodes, it makes you a little bit worried you’re going to get up there and find disease stuck on the axillary vein that you can’t take out. And knowing that the patient is HER2-positive and knowing that the response rate to neoadjuvant therapy with anti-HER2 agents is so high, to me this is a particularly favorable subset of patients to give neoadjuvant therapy to. I think that would be a perfectly appropriate approach, but as a surgeon we’re a little touchy about the definition of “inoperability.”

DR LOVE: Sara, what would you be thinking at this point?

DR HURVITZ: There are several regimens that are available for neoadjuvant HER2-positive breast cancer. But regardless of which regimen you wanted to use, my preference would be to give a regimen where you would be giving the trastuzumab up front. Rather than doing 4 cycles of AC or 4 cycles of FEC followed by trastuzumab, these are patients that I’d try and get on trastuzumab. In my own practice, I’ll use the TCH regimen. Again, about half of the patients have pathologic complete response rate. It’s nice. You’re going to be able to follow them clinically. If they’re not responding, you can switch therapy.

DR LOVE: What about pertuzumab? What about lapatinib?

DR HURVITZ: I have, as I alluded to earlier, a clinical trial looking at TCH plus lapatinib. And the dose that we were able to give on the clinical trial was 1,000 milligrams of lapatinib. But many patients have to be dose-reduced because of diarrhea, as we’ve all discussed. It does seem to increase the pathologic complete response rate in patients who can tolerate it and stay on the therapy.

Pertuzumab, I would love to add it in the context of a clinical trial. We will be doing so in the next year but could not get it for this patient outside of that.

DR LOVE: If you could get it, would you use it?

DR HURVITZ: Should I use it? No, not outside of a clinical trial. Would I be tempted to use it? Yes.

DR LOVE: Hope, how would you think this through?

DR RUGO: Very similarly, I think, to everyone else. We would treat this patient with neoadjuvant therapy starting with weekly paclitaxel and trastuzumab because we’re more for ACT in high-risk patients who are young enough and have good enough heart to get it. We would give weekly paclitaxel with trastuzumab for 12 weeks and then followed by dose-dense AC. I don’t think we know that you need to give it dose dense. Then followed by surgery, the patient obviously had surgically accessible disease initially.

I think the issue about adding lapatinib or adding pertuzumab, most of us have been thinking about that. And I think pertuzumab is really too new for us to have gotten to that yet in the early-stage setting. But our patients who seem like they’re not doing well, then we would have — I think probably all of us — a relatively lower threshold for trying to add something that we think is effective.

DR LOVE: What happened with this patient, Bill?

DR GRADISHAR: She was started on TCH.