Update on HER2-Targeted Therapy in Early Breast Cancer - Episode 2

Neoadjuvant Approaches for Early-Stage HER2+ Breast Cancers

Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH: Generally speaking, we have shifted pretty dramatically toward preferring preoperative therapy for our patients with HER2 [human epidermal growth factor receptor 2]–positive disease. This allows us to assess response to therapy and potentially adapt our adjuvant treatment after surgery based on this response. Adapting treatment based on response can, therefore, improve outcomes. So it’s pretty important to offer preoperative therapy to patients who are candidates.

We generally consider giving preoperative treatment to anyone with a tumor that’s either over 2 cm or has lymph node involvement. This is where a multidisciplinary conversation is pretty important. You need to assess this scenario with your surgical colleagues. Do they feel that the patient could potentially have a breast cancer–conserving surgery? Are they someone who is a candidate for mastectomy? How could that potentially change given the response to preoperative therapy? So we usually communicate with our surgeons and radiation oncologists up front, prior to making this decision.

But generally speaking, we do tend to give systemic treatment to those patients who have tumors that are over 2 cm or have lymph node positivity. If they’re smaller than 2 cm and have no lymph node involvement, then we often consider taking them to surgery up front.

When thinking about which systemic therapy to give in the preoperative setting, the 2 standard regimens are TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab], given every 3 weeks for 6 cycles, or a regimen that involves giving Adriamycin [doxorubicin] and Cytoxan [cyclophosphamide] followed by either paclitaxel or docetaxel with trastuzumab and pertuzumab.

We do prefer to use a nonanthracycline-based regimen, given that we see lower rates of cardiac toxicity and leukemia when we omit the anthracycline. Most of the time we tend to prefer using the TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] regimen up front, prior to surgery. In terms of how patients actually do based on their responses to preoperative therapy, we do know that patients who achieve a pCR [pathologic complete response] have better outcomes than those who failed to achieve a pCR. Patients who achieve a pCR tend to have rates of recurrence that range somewhere from 10% to 14%, at most. Those rates are continuing to go down as our systemic therapy continues to improve.

Generally speaking, we do know that pathologic complete response rates are higher in patients who have hormone receptor–negative HER2-positive cancers relative to those patients with hormone receptor–positive HER2-positive disease. This is true regardless of the regimen that is selected. Again, this is consistently seen across trials.

However, when you look at long-term outcomes for patients, we do see that over time, despite seeing differences in rates of pCR in these 2 groups, long-term outcomes are actually quite similar. While we know that the hormone receptor–positive HER2-positive patients tend to have lower rates of pCR, long-term outcomes do seem to be fairly similar to the hormone receptor–negative patients.

Transcript edited for clarity.