Neoadjuvant pembrolizumab-based therapy versus dual HER2 blockade in early breast cancer: comparable surgical complication rates in a real-world cohort.

BACKGROUND: Neoadjuvant systemic therapy (NST) has become a cornerstone in the management of aggressive early breast cancer (BC) subtypes, including triple-negative (eTNBC) and HER2-positive disease. Immune checkpoint inhibition with pembrolizumab represents an active immunotherapeutic approach, whereas dual HER2 blockade with trastuzumab and pertuzumab constitutes passive immunotherapy in early HER2-positive BC. Although both strategies demonstrate substantial antitumor efficacy, real-world data directly comparing their surgical safety profiles are limited. MATERIALS AND METHODS: This retrospective single-center cohort study included 99 patients with early BC treated with NST between 2014 and 2025. A total of 33 patients with TNBC received pembrolizumab-based therapy according to the KEYNOTE-522 regimen, whereas 66 patients with HER2-positive disease received chemotherapy combined with trastuzumab and pertuzumab. Surgical adverse events within 30 days postoperatively were assessed using the Clavien-Dindo classification and the Comprehensive Complication Index (CCI). Complication rates and severity were compared between groups. RESULTS: The overall postoperative complication rate was 25.3%, with no significant difference between TNBC and HER2-positive cohorts (27.3% vs. 24.2%, p = 0.744). Most complications were minor (Clavien-Dindo ≤II), and rates of major complications (≥IIIa) did not differ between groups (p = 0.706). Mean CCI scores were comparable (22.1 vs. 24.4; p = 0.630). Seroma formation was the most frequent adverse event in both cohorts. In an exploratory multivariable logistic regression analysis, treatment group was not independently associated with postoperative complications. Pathological complete response rates were 63.6% in TNBC and 45.5% in HER2-positive patients. No clinically relevant delays in adjuvant radiotherapy occurred. CONCLUSION: No statistically significant differences in postoperative morbidity were observed between treatment groups. These findings support the feasibility of integrating both neoadjuvant treatment strategies into routine surgical practice; however, confirmation in larger prospective studies is warranted.