Management of HER2-Positive Breast Cancer After Neoadjuvant Therapy

Rationale for Neoadjuvant Pertuzumab

The American Society of Clinical Oncology and other guideline societies support the use of pertuzumab combined with trastuzumab and chemotherapy for neoadjuvant treatment of HER2-positive early-stage breast cancer, based on significantly improved pathological complete response (pCR) rates in the NeoSphere and TRYPHAENA trials 1, 2, 3.
The NeoSphere trial demonstrated that pertuzumab plus trastuzumab and docetaxel achieved a 45.8% pCR rate compared to only 29% with trastuzumab plus docetaxel alone (P=0.0063) 1, 4.
The mechanism of dual HER2 blockade works by complementary binding: pertuzumab and trastuzumab bind to different epitopes of the HER2 receptor, providing greater antitumor effect when administered together in the preoperative setting 2, 5.

For patients who achieved pCR after neoadjuvant therapy, the European Society for Medical Oncology (ESMO) 2019 guidelines recommend completing 1 year of trastuzumab-based therapy, with dual blockade (trastuzumab/pertuzumab) considered only for high-risk patients (node-positive or ER-negative) for the full year duration starting before or after surgery 8.
The 2023 St. Gallen consensus indicates that patients achieving pCR after neoadjuvant chemotherapy with trastuzumab and pertuzumab should continue anti-HER2 therapy for a total duration of 1 year, but there was no consensus whether to continue with trastuzumab alone or with pertuzumab and trastuzumab 7.
Importantly, the addition of pertuzumab to trastuzumab in the post-neoadjuvant setting need not be routinely considered for clinically node-negative tumors at baseline that achieve pCR 7.

If pertuzumab was NOT used in neoadjuvant therapy and pCR was achieved, complete 1 year total of trastuzumab-based therapy without adding pertuzumab post-operatively, as recommended by ESMO and other guideline societies 8, 7.
For patients with residual disease after neoadjuvant therapy, switch to adjuvant T-DM1 for 14 courses, as recommended by ESMO and other guideline societies 8, 7.

Cardiac monitoring remains mandatory throughout trastuzumab therapy regardless of whether pertuzumab was used, as trastuzumab carries cardiotoxicity risk 8, 6.
The optimal scenario is to use dual HER2 blockade (pertuzumab + trastuzumab) from the start in the neoadjuvant setting for stage II-III HER2-positive breast cancer, as this maximizes pCR rates and improves long-term outcomes 7, 9.