Patient Profile 1: Early Stage HER2+/HR+ BC


Virginia G. Kaklamani, MD, DSc, presents a patient profile of early stage HER2+ breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery.


Sara Hurvitz, MD: Now I want to get into a couple of patient profiles that will help us talk and think through how we approach real-world patients. So to start, Dr Kaklamani, Virginia, can you present your patient?

Virginia G. Kaklamani, MD, DSc: Sure. This is a 56-year-old patient who did not have any comorbidities. She was found to have a 2.4 cm left-breast mass and enlarged lymph nodes. Both [of those] were biopsied. She had triple-positive disease, and so she received neoadjuvant TCHP [docetaxel, carboplatin, trastuzumab and pertuzumab]. She had minimal grade 1 neuropathy, but otherwise did pretty well. At the time of surgery she was found to have pCR [pathologic complete response] in the breast, but she did have 1 positive adenoid lymph node.

Typically, we don’t repeat IHC [immunohistochemistry] staining between the diagnosis and surgery, but if a patient had their initial IHC at an outside institution our policy is to repeat it. So we did repeat it here. She was still ER/PR+, HER2 was 2+, and the FISH [fluorescence in situ hybridization] was negative. So the question now is, what do we do with this patient?

Sara Hurvitz, MD: [It] is so great to address this issue because I can’t tell you how many times I’ve seen that. We do test biomarkers on the residual disease at my institution. Are you doing that at your institutions as well? Yes [for] Melinda. Debu?

Debu Tripathy, MD: We do not do it routinely, but it sometimes gets done. We reported that it’s as high as 30%. And in our series, patients did worse, but there have been some other series where those patients did not do worse. So I don’t know that we know what the meaning of it is. I generally go by the first [results], and I don’t modify treatment because I don’t know how to. Now, I will add that in patients that are at very high risk, and I think they have had a biphenotypic tumor from the beginning, I might consider anthracycline-based therapy. I’ve only done that a couple of times when I think they have really high-burden disease and might need anthracyclines. But there’s not a lot of data to guide us on that.

Sara Hurvitz, MD: Have you had this situation? Do you ever go back and retest the original tumor?

Heather McArthur, MD: We do much to my frustration in the end. We do have subset, exploratory data, from KATHERINE [trial] that indicates that even patients who did convert to HER2 still seem to derive benefit from adjuvant T-DM1 [trastuzumab emtansine]. We just published our own experience looking at this exact question, specifically patients who lost HER2 positivity, and they still seem to derive the same benefit from HER2-directed therapy. So I’m not sure what information it’s necessarily adding. It’s certainly not directly informing treatment decisions in this space, but it might make me lean in more to the hormone-directed therapy for that patient.

Sara Hurvitz, MD: Interesting. I was going to ask, if you really were convinced this was biphenotypic, that there were 2 different foci, [and] it was very high-risk disease, if you would be a little more aggressive with hormonal therapy or even consider a CDK4/6 inhibitor. So what happened, Virginia?

Virginia G. Kaklamani, MD, DSc: The data from KATHERINE suggests that regardless of HER2 status at the time of surgery that patients benefited from T-DM1. So I did give her T-DM1. I’m waiting to see what I’m going to do next. I don’t know because now you have the neratinib question, and you also have the CDK4/6 inhibitor question. I think I’m leaning [more] toward neratinib, but this is tricky.

Sara Hurvitz, MD: Yes, indeed. If you were going to do the CDK4/6 inhibitor, this is a data-free zone, and would be entirely the art of medicine, and not really on-label. Would you give it, after the T-DM1, a CDK4/6 inhibitor?

Virginia G. Kaklamani, MD, DSc: I would not combine it with T-DM1.

Sara Hurvitz, MD: That makes sense. That was a fabulous case and some really important points [were made].

Transcript edited for clarity.

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