Abbreviated THP (paclitaxel+trastuzumab+pertuzumab) drives 99% 5-year EFS in stage II–III HER2+ breast cancer

In the single-arm Phase 2 DAPHNe trial secondary analysis (NCT03716180), patients with stage II–III ERBB2(HER2)-positive breast cancer received 12 weeks of neoadjuvant paclitaxel plus dual HER2 blockade with trastuzumab and pertuzumab (THP), then surgery with adjuvant therapy tailored to pathologic response (n=98; 92.9% stage II; 66.3% HR+). At median 5.2-year follow-up, 5-year event-free survival was 99% (95% CI, 97%-100%), recurrence-free interval 98% (95% CI, 93%-100%), distant RFI 100% (95% CI, 100%-100%), and overall survival 99% (95% CI, 97%-100%); this looks at least comparable to modern multi-agent neoadjuvant chemo+HP benchmarks in stage II–III disease (e.g., TRAIN-2 3-year EFS ~93%-94%), albeit with cross-trial caveats and a markedly less intensive chemo backbone. In an ultrasensitive whole-genome, tumor-informed ctDNA substudy (n=57), baseline ctDNA was detected in 89.5% and cleared preoperatively in 96.1% (49/51), with <10% detectability postoperatively; the lone local recurrence had ctDNA positivity at recurrence and cleared after resection.