The Future of Early HER2-Positive Management

Ruth O’Regan, MD:Overall, I think patients with early HER2 [human epidermal growth factor receptor 2]—positive breast cancer are really doing very well with the regimens that we have right now. The preoperative approach is very attractive because you have this surrogate marker of outcome with the response to the preoperative treatment. And the question, I think, for HER2-positive breast cancer was really 2-fold. There are patients [who] don’t get a pathologic complete response. What do you do with those patients? Obviously, they have cancers that may be somewhat resistant.

We now have very exciting results from the KATHERINE study showing that trastuzumab DM1 [emtansine] can markedly improve outcome for those patients. But even with that, there may be patients [who] still have recurrences. And there are a number of new agents coming down the pipeline. Most of them are antibody-based immunotherapy-based regimens that I think will be very exciting going forward. They’re all being [evaluated] in the metastatic setting, but they may end up being translated into the early-stage setting for selected patients, I think.

One of the other big questions for early-stage HER2-positive breast cancer is, can we further de-escalate therapy for patients? So we already know for patients with stage I breast cancer that’s HER2-positive that you can treat them with the APT [adjuvant paclitaxel and trastuzumab] regimen, which is essentially 12 weeks of paclitaxel with trastuzumab. The bigger question is, are there a group of patients who maybe don’t need chemotherapy at all? And the most likely candidates would be patients with HER2-positive, hormone receptor—positive breast cancer where potentially we may be able to omit chemotherapy and just give them endocrine therapy with HER2-directed therapy.

The trials that have looked at this previously, mainly in the preoperative setting, haven’t shown definitively a group of patients [for whom] we can omit chemotherapy, but I do think this is a very important research question going over.

As we talked about earlier, there is a subset of these hormone receptor—positive, HER2-positive breast cancers that are actually luminal A cancers. And if we could delineate which patients have those cancers, they may be better treated with endocrine therapy and HER2-directed therapy versus chemotherapy, because there is substantial cross talk between the ER [estrogen receptor] and HER2 pathways, [and] it may be more important to block those pathways rather than give chemotherapy.

But currently there really is no group of patients right now [whom] we would omit chemotherapy from, apart from patients who have very small HER2-positive cancers. So T1a cancers, for example. [For] most of those patients we generally do not give chemotherapy in HER2-positive, HER2-directed therapies. But there may be other groups of patients where we can omit chemotherapy as well.

I think [there are] very important research questions that we’ll evaluate going forward.

Transcript edited for clarity.

Case: A 52-Year-Old Woman withHER2+ Breast Cancer

H & P

• A 52-year-old, postmenopausal woman presented with a mass in her left breast at her annual gynecologic exam; was referred to oncology
• 2 children, menopause at age 49
• No history of cardiovascular disease, no family history of breast cancer
• PE: reveals a slightly overweight woman (BMI = 26 kg/m²), with palpable masses in left breast and left axillary nodes

Imaging

• Mammogram reveals 2.5-cm tumor in left breast
• CT: confirms tumor in left breast and left axillary node involvement (2.6-mm metastasis in 1 node)

Biopsy and labs:

• Histology: invasive ductal adenocarcinoma
• Histologic grade: G2
• ER (-)/ PR (-)
• HER2IHC, 3+
• BRCA1/2status: unknown

Treatment

• She received neoadjuvant TCH-P (docetaxel + carboplatin + trastuzumab + pertuzumab) and achieved pathologic complete response
  • Developed grade 3 diarrhea during second cycle of chemotherapy, which required a one-level dose reduction of paclitaxel
  • Diarrhea resolved to grade 1/2
• Underwent breast-conserving surgery and removal of left axillary lymph nodes; no residual disease
• Currently completing adjuvant therapy; trastuzumab + pertuzumab (total 18 cycles)