Is Neoadjuvant Chemotherapy Necessary for Male Breast Cancer? A SEER-Based Population Study

Neoadjuvant chemotherapy (NAC) is widely utilized in female breast cancer to achieve disease downstaging, reduce distant dissemination, and assess chemosensitivity. However, the efficacy of NAC in male breast cancer (MBC) remains poorly understood. This study aimed to evaluate pathologic complete response (pCR) rates and overall survival (OS) outcomes following NAC in MBC patients, stratified by tumor subtype.

Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for MBC patients who received NAC between 2000 and 2020. Patients were categorized by receptor status: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), HR+/HER2+, HR-/HER2+, and HR-/HER2-. The proportions of pCR (ypT0/Tis ypN0) were compared across subtypes. OS was estimated using the Kaplan-Meier method, and differences were analyzed using the log-rank test. Propensity score matching (PSM) was applied to reduce selection bias inherent to this retrospective observational study. Based on the baseline characteristics of breast cancer patients who received NAC, univariate Cox proportional hazards regression analysis was first performed to screen potential prognostic variables. Covariates with statistically significant differences in the univariate model were subsequently incorporated into the multivariate Cox regression model to identify independent risk factors associated with OS prognosis. Statistical analyses were performed using STATA 12.0 and SPSS Version 23.0.

A total of 260 MBC patients who received NAC were included in the analysis. No statistically significant difference in OS was observed between MBC and FBC patients receiving NAC (HR = 1.067; 95% CI: 0.929-1.226; p = 0.358). However, female patients had a better OS (HR = 0.930; 95% CI: 0.913-0.948; p < 0.001) after PSM. Five-year OS for MBC patients with pCR versus non-pCR was 92% vs. 77.3% (HR = 1.236; 95% CI: 0.787-1.942; p = 0.357). The results were further confirmed in the multivariate Cox regression model after PSM, in which pCR can be considered an independent prognostic factor. In addition, adjuvant chemotherapy demonstrated superior OS compared to NAC in MBC patients (HR = 3.223; 95% CI: 2.772-3.747; p < 0.001). The proportions of pCR by tumor subtype were as follows: (i) HR-/HER2+: 50.0% (n = 3), (ii) HR-/HER2-: 41.7% (n = 5), (iii) HR+/HER2+: 10.7% (n = 7), and (iv) HR+/HER2-: 5.5% (n = 9). OS was significantly worse with NAC compared to adjuvant chemotherapy in both HR+/HER2- (HR = 1.363; 95% CI: 1.129-1.646; p = 0.001) and HR+/HER2+ (HR = 1.951; 95% CI: 1.449-2.627; p < 0.001) subtypes. However, no statistically significant differences were observed in HR-/HER2+ (HR = 2.296; 95% CI: 0.807-6.538; p = 0.119) and HR-/HER2- (HR = 1.758; 95% CI: 0.847-3.649; p = 0.130).

This population-based study demonstrates that MBC patients receiving NAC achieved significantly lower pCR rates compared to female patients. The HR+/HER2- and HR+/HER2+ subtypes exhibited greater resistance to NAC. Furthermore, achieving pCR was not prognostic for improved survival in MBC. These findings suggest that NAC may not be necessary for all MBC cases. Future research should explore alternative treatment strategies tailored to the unique biological characteristics of MBC.