De-escalation of Treatment of HER2 Positive Breast Cancer after Pathological Complete Response to Neoadjuvant Chemotherapy; a Retrospective Analysis

Abstract Background The teatement of choice for the neo-adjuvant treatment of HER2-positive early breast cancer includes trastuzumab–pertuzumab (TP) with chemotherapy. For those achieving pathological complete response (pCR), the optimal adjuvant strategy remains less clearly defined. Method We retrospectively included patients with HER2-positive early or locally advanced breast cancer who achieved pCR after neo-adjuvant TP-based chemotherapy between January 2021 and December 2023. Disease-free survival (DFS), overall survival (OS), and cardiac dysfunction were assessed. Results A total of 356 patients were included: 86 (24.2%) received adjuvant trastuzumab and 270 (75.8%) received adjuvant trastuzumab–pertuzumab. After a median follow-up of 24.8 months, the estimated 3-year DFS for the overall cohort was 89.8%. DFS did not significantly differ between the trastuzumab arm (87.7%) and the dual blockade arm (90.5%) (log-rank p = 0.2213).In subgroup analyses, clinical N3 disease and younger patients less than 40 years derived a significant benefit from dual blockad.No other significant differences in DFS were detected across subgroups defined by clinical T stage, hormone receptor status, HER2 IHC score, tumor grade, or Ki-67 index.Cardiac safety was consistent with previous reports, with no significant difference in dysfunction between trastuzumab (23.8%) and trastuzumab–pertuzumab (18.1%) (p = 0.922). Conclusions Among patients who achieved pCR following neo-adjuvant TP-based chemotherapy, de-escalation to adjuvant trastuzumab monotherapy appears to be a safe strategy that does not compromise DFS in most cases.