Gender Disparities in Response to Neoadjuvant Therapy for Early-Stage Breast Cancer: A Propensity Score-Matched Analysis of the SEER Database

Background: Male breast cancer (MBC) is a rare disease, and its management has historically been extrapolated from data on female breast cancer. Evidence regarding the efficacy of neoadjuvant therapy in men and possible gender-based differences in treatment response remains limited. This study aimed to compare neoadjuvant therapy efficacy between men and women using a large, population-based database. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2022) were analyzed. Patients with early-stage breast cancer who received neoadjuvant therapy were identified. Propensity score matching (PSM, 1:4 ratio) was performed to balance demographic and clinicopathological variables between male and female patients. Objective response rate (ORR) and overall survival (OS) were compared using χ² tests and Kaplan–Meier analyses, respectively. Results: Among 55,549 eligible patients, 224 were male and 55,325 were female. After PSM, baseline characteristics were well balanced. Male patients demonstrated a significantly lower ORR compared with female patients (82.1% vs. 87.7%, p = 0.028), with the greatest disparity observed in the HER2-positive subgroup (84.2% vs. 94.6%, p = 0.003). However, among patients who achieved an objective response, OS did not differ significantly between genders (median OS 137 months vs. not reached, p = 0.228). Conclusion: Men with early-stage breast cancer exhibit lower responsiveness to neoadjuvant therapy than women, particularly in HER2-positive disease. However, survival equivalence among responders underscores the continued value of neoadjuvant therapy in MBC.