Clinicopathological Features and Prognostic Implications of HER2-Low in Early-Stage Male Breast Cancer: A Retrospective Analysis

Background: The clinicopathological and prognostic features of HER2-low female breast cancer (BC) patients have been widely studied. Current knowledge suggests that low HER2 expression could be identified as a special entity for treatment. However, research on HER2-low in early-stage male breast cancer remain limited. Methods: This retrospective study screened male BC patients at a single institution between January 2010 and September 2023. Early-stage cases with non-HER2-positive tumors were included and categorized into HER2-low and HER2-zero groups. Clinicopathological features were collected and compared between the two groups. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Statistical analysis was conducted viadescriptive statistics, the Kaplan‒Meier method with the log-rank test, and the Cox proportional hazards model to evaluate differences in DFS and OS between the groups. Results: In 99 early-stage non-HER2-positive male BC patients, 41 were classified as HER2-low, and 58 were classified as HER2-zero. In terms of clinicopathological features, the HER2-low subgroup exhibited higher androgen receptor (AR) expression (P=0.003). In terms of survival, no significant difference was observed in DFS (P=0.1), but the HER2-low subgroup had a significantly longer OS than the HER2-zero subgroup (P=0.01). Multivariate analysis revealed that age and TNM stage wereindependent prognostic factors for DFS, whereas age and HER2-low status were independent prognostic factors for OS. Conclusion: In early-stage male BC, the HER2-low population differed in clinicopathological features and prognostic role compared to HER2-zero counterparts. Compared with the HER2-zero subgroup, the HER2-low subgroup had a better OS, and HER2-low status was determined to be an independent prognostic factor for OS but not for DFS.