Prognostic impact of HER2-low expression in HER2-negative breast cancer under different hormone receptor status

HER2-low expression in breast cancer has received increasing attention as a target for novel antibody-drug conjugates (ADCs). The purpose of this study was to investigate the impact of HER2-low status on survival outcomes in patients with HER2-negative early breast cancer.

Medical records of patients with HER2-negative non-metastatic breast cancer who were treated at our institution from January 2008 and June 2019 were retrospectively reviewed. The main outcome measurements of our study were overall survival (OS) and disease-free survival (DFS), which were compared between the HER2-low and HER2-0 groups stratified by hormone receptor (HR) status.

A total of 2605 HER2-negative cases were identified, of which 1418 (54.4%) had HER2-low and 1187 (45.6%) had HER2-0 disease. The proportion of HER2-low tumors was significantly higher in HR-positive tumors than in HR-negative tumors. No significant difference was observed in DFS and OS between the HER2-low and HER2-0 groups in univariate analyses, regardless of HR status. Multivariate analysis of the Cox proportional hazard regression model revealed that HER2-low was independently associated with improved OS in patients with HR-negative disease (HR 0.32, 95% CI 0.13-0.80, p = 0.015).

Our findings demonstrate that the prognostic impact of low HER2 expression varies according to HR status, with slightly favorable outcomes among HER2-low tumors in patients with HR-negative disease.