Prognostic Impact of HER2 Low Status in Male Breast Cancer: Prospective Cohort Analysis.

Simple Summary: Male breast cancer (MBC) is a rare condition, and the role of low HER2 expression (HER2 low) is not well understood. In this prospective study, 870 MBC patients treated between May 2009 and June 2023 were evaluated to investigate the prognostic significance of HER2 low status. After a median follow-up of 43 months, 659 patients were classified into three groups: 76% were HER2 low, 12.3% were HER2 zero, and 11.7% were HER2 positive. HER2 positivity was linked to younger age, higher tumor proliferation, and more aggressive cancer characteristics, but no differences were found between HER2 zero and HER2 low groups. Furthermore, HER2 low status did not influence disease-free or overall survival. However, HER2 low has a potential clinical impact on MBC as a treatment target. Background: Male breast cancer (MBC) is a rare disease, and the potential influence of low expression of human epidermal growth factor receptor 2 (HER2 low) remains unexplored. Methods: In this prospective cohort study, we evaluated 870 patients treated for MBC between May 2009 and June 2023 to assess HER2 low status and its prognostic implications. Results: With a median follow-up of 43 months (range 1–175 months), 659 eligible patients were categorized into three groups based on HER2 status: 501 (76%) HER2 low, 81 (12.3%) HER2 zero, and 77 (11.7%) HER2 positive. HER2 positivity correlated with younger age, higher proliferation index, non-specific type histology, lymphovascular invasion (LVSI), and low differentiation grade. Notably, all these parameters were equally distributed between the HER2 zero and HER2 low groups. Additionally, HER2 positivity was significantly associated with increased occurrences of regional and distant lymph nodes and pulmonary metastases. However, no statistically significant difference was observed between HER2 zero and HER2 low. Disease-free and overall survival showed no significant disparities between the groups. Conclusions: Our findings suggest that HER2 low status is frequently detected in MBC. Despite this, HER2 low did not correlate with clinical and pathological parameters, nor did it impact patients' survival. [ABSTRACT FROM AUTHOR]