Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

Introduction: Patients with ERBB2(HER2)-positive breast cancer experience high rates of pathologic complete response (pCR) to neoadjuvant systemic therapy. Here we aimed to examine axillary nodal response to neoadjuvant dual HER2-targeted therapy in a multi-institution clinical trial. Methods: A single-arm Phase II prospective trial (Metzger, Cancer Discov. 2021 Oct;11(10):2474-2487) treated HER2-positive breast cancer patients with 6 cycles of neoadjuvant T-DM1 plus Pertuzumab. Rates of pathologic nodal disease in clinically node-negative (cN0) and node-positive (cN1) patients were analyzed, stratified by residual breast disease (pCR and residual cancer burden [RCB] I-III). Results: A total of 158 patients completed treatment on-trial followed by axillary surgery. Of 92 cN0 patients, 46 (50.0%) experienced breast pCR, 84 (91.3%) were pathologically node negative (ypN0). Of 46 cN0 with breast pCR and 10 with RCB of I, 100% were ypN0. Of 36 with RCB of II-III, 28 (77.8%) were ypN0. 85 (92.4%) underwent sentinel lymph node biopsy (SLNB) and 7 (7.6%) axillary lymph node dissection (ALND). Of 66 cN1 patients, 34 (51.5%) experienced breast pCR, 44 (66.7%) were ypN0. Of 34 cN1 with breast pCR, 30 (88.2%) were ypN0. Of 8 with RCB of I, 100% were ypN0. Of 24 with RCB of II-III, 6 (25.0%) were ypN0. 22 (33.3%) underwent SLNB and 44 (66.7%) ALND. Conclusion: HER2-positive patients treated with dual HER2-targeted therapy were frequently ypN0 if they experienced pCR or RCB I of the breast. These findings support minimal axillary surgical staging for HER2-positive breast cancer patients who experience pCR or RCB I in trials of investigational HER2-targeted regimens.