12-Week Dual-HER2 ± Paclitaxel Delivers 97% 5-Yr OS in De-Escalated HER2-Positive Early Breast Cancer

A pooled analysis of 713 patients from three trials (NCT01817452, NCT01779206, NCT03272477) tested short-course neoadjuvant regimens—trastuzumab + pertuzumab with or without 12 weekly paclitaxel, or antibody–drug conjugate T-DM1 ± endocrine therapy—followed by surgery and chemo only for non-pathologic complete response (pCR) cases. After a 60.7-month median follow-up, five-year overall survival was 98% with paclitaxel plus dual HER2 blockade and 97% with antibody-only neoadjuvant treatment Invasive DFS (iDFS) reached 96% vs 88% (HR 0.56, p = 0.08). pCR occurred in 66% of paclitaxel-treated versus 31% chemo-free patients; those achieving pCR enjoyed 5-year iDFS of 98% (with chemo) and 94% (chemo-free). Historical one-year trastuzumab after full anthracycline/taxane chemotherapy yields ~69% 10-year DFS and higher cardiotoxicity, underscoring the toxicity savings of this 12-week approach.