HER2-low breast cancer in men: clinical characteristics and prognosis

Background: Breast cancer is rare in men, and the incidence and clinical significance of human epidermal growth factor receptor 2 (HER2)-low and HER2-0 status remain poorly understood. Our single-institution retrospective cohort study examined the incidence of HER2-low and HER2-0 in male breast cancer and its effect on disease-free survival (DFS).

Methods: Clinicopathologic data were abstracted from a chart review of men with breast cancer treated at Dana-Farber Cancer Institute from January 2007 to February 2024. The primary outcome was DFS, defined as the period from surgery to breast cancer recurrence or death. Due to the limited number of events, analyses were descriptive/exploratory and included Kaplan-Meier estimates, log-rank testing, and unadjusted Cox models. Overall survival (OS) was evaluated secondarily. Oncotype DX recurrence score (RS) data were summarized descriptively in the subset with available results.

Results: Among 64 male patients with breast cancer, 49 (76.6%) had HER2-low, 9 (14.1%) had HER2-0, and 6 had HER2-positive (9.4%) disease at primary diagnosis. We observed no statistically significant difference in DFS between HER2-low and HER2-0 patients [unadjusted hazard ratio (HR): 0.39, 95% confidence interval (CI): 0.07–2.05; P=0.27]. Oncotype DX RS was available for 32 patients (55.2%), including 30 HER2-low and 2 HER2-0 cases.

Conclusions: HER2-low disease was common in this single-institution male breast cancer cohort. Because of the small sample size, limited event count, and absence of central pathology review, survival comparisons between HER2-low and HER2-0 disease should be interpreted as exploratory and should not be taken as evidence of equivalence.