PURPOSE: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined subgroup of HER2-negative breast cancer. It is unknown whether HER2-low status is associated with brain metastases (BrM) development. We aimed to determine the association between HER2-low status and the time to developing BrM. METHODS: HER2 status was determined in a cohort of 689 women with metastatic breast cancer (MBC) who underwent treatment for BrM at Sunnybrook Odette Cancer Centre from 2008 to 2018. In patients with primary breast cancer (PBC) HER2 subclassification available (subgroup 1), we investigated time from PBC diagnosis to BrM diagnosis (PBC-time to brain metastases [TTBM]). In patients with HER2 subclassification available in any tissue (subgroup 2), we investigated time from MBC diagnosis to BrM diagnosis (MBC-TTBM). RESULTS: In subgroup 1 (n = 175), patients with HER2-low disease (n = 42) had a shorter PBC-TTBM compared with those with HER2-zero disease (n = 77
hazard ratio, 2.4
CONCLUSION: Our findings suggest that among patients with HR+ breast cancer, HER2-low status was associated with shorter TTBM compared with HER2-zero status. In a subset of patients for whom HER2 status of the PBC was available, HER2-low status was associated with shorter PBC-TTBM, irrespective of HR status. This study suggests a previously unrecognized association between HER2-low status and timing of BrM development.