Neoadjuvant paclitaxel, trastuzumab, and pertuzumab for stage II-III HER2-positive breast cancer: secondary analysis of DAPHNe

The neoadjuvant combination of paclitaxel, trastuzumab, and pertuzumab (THP) represents a promising abbreviated regimen for early-stage HER2-positive breast cancer, but long-term outcomes and the role of ultrasensitive circulating tumor DNA (ctDNA) monitoring are incompletely defined. Secondary analysis of the multicenter phase 2 DAPHNe trial assessed 5-year outcomes with 12 weeks of neoadjuvant THP for stage II-III HER2-positive breast cancer in 98 patients. The 5-year recurrence-free interval rate was 98% (95% CI 93-100) and the five-year overall survival rate was 99% (97-100). Among 57 patients included in ctDNA analysis, baseline ctDNA was detected in 51 patients (89.5%) with clearance after neoadjuvant THP in 49 of 51 patients (96.1%) with only 2 (3.9%) remaining ctDNA-positive preoperatively.; detectability remained low (<10%) during postoperative follow-up. One patient experienced a local recurrende, with ctDNA detected at time of recurrence and cleared following surgical resection. The authors conclude that in this secondary analysis of DAPHNe, neoadjuvant THP was associated with excellent long-term outcomes in patients with early-stage HER2-positive breast cancer. Ultrasensitive ctDNA analyses demonstrated high baseline detection rates an near-universital clearance after abbreviated neoadjuvant therapy, supporting further investigation of ctDNA-guided de-escalation strategies in this setting.