HR+/HER2- breast cancer brain metastases treated with definitive local therapy: a focus on endocrine sensitivity and incidence of leptomeningeal disease

Abstract Background Brain metastases (BrM) among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) are under-studied. We sought to understand the endocrine sensitivity of patients with HR+/HER2- BrM and determine associated risk of leptomeningeal metastatic disease (LMD). Methods We conducted a retrospective cohort study of 204 consecutive patients (≥18 years of age) with HR+/HER- mBC who were treated for BrM at the Sunnybrook Odette Cancer Centre between 2008-2018. We used descriptive statistics to summarize patient and treatment characteristics and Kaplan-Meier analyses for survival outcomes. The log-rank test was used to compare outcomes of patients with endocrine sensitive versus endocrine resistant disease. Results Among 204 patients with HR+/HER2- BrM, the median age at BrM diagnosis was 56 years (range, 48-64) and the median time between diagnosis of mBC to development of BrM was 15 months (interquartile range IQR, 3-36). At the time of BrM development, 160 patients (78.4%) had endocrine resistant and 28 patients (13.7%) had endocrine sensitive disease; endocrine sensitivity of the remaining 16 patients (7.8%) was unknown. In total, 58 patients (28.4%) developed LMD with a median time from BrM to LMD of 10.8 months (IQR 3.1—14.8).Patients with endocrine sensitive disease at time of BrM diagnosis had a a longer brain-specific progression-free survival (7 months versus 5 months, p = 0.004) and overall survival (24 months versus 5 months, p = 0.002) compared to those with endocrine resistance. Conclusions Most patients with HR+/HER2- BrM have endocrine resistant disease, with an unexpectedly high likelihood of developing LMD.