On the phase 2 DAPHNe trial 98 patients with predominantly stage II HER2-positive breast cancer received 12 weeks of neoadjuvant paclitaxel, trastuzumab, and pertuzumab (THP) with further chemotherapy reserved for those who did not achieve a complete pathologic response (n=33). This means the only chemo received by two-thirds of patients was 12 weeks of Taxol. Outcomes were nearly perfect: zero distant recurrences and a single local recurrence occurred within 5 years. In a prespecified biomarker analysis of 57 patients, baseline ctDNA was detectable in nearly 90% using an ultrasensitive, tumor-informed assay. After THP, 96% of ctDNA-positive patients cleared detectable disease before surgery, and ctDNA remained detectable in fewer than 10% during postoperative surveillance. The lone local recurrence was accompanied by re-emergence of ctDNA, which again became undetectable following surgical salvage. Notably, ctDNA clearance did not predict pathologic complete response considering almost everyone cleared. | Tarantino, JAMA Oncol 2026

