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 understudied. We sought to understand the endocrine sensitivity of patients with HR+/HER2– BrM and determine the associated risk of leptomeningeal metastatic disease (LMD). Methods We conducted a retrospective cohort study of 204 consecutive patients (≥18 yr of age) with HR+/HER– mBC who were treated for BrM at the Sunnybrook Odette Cancer Centre between 2008 and 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 disease, 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 the time of BrM diagnosis had a longer brain-specific progression-free survival (7 mo versus 5 months, P = .004) and overall survival (24 months versus 5 mo, P = .002) compared with those with endocrine resistance. Conclusions Most patients with HR+/HER2– BrM have endocrine-resistant disease, with an unexpectedly high likelihood of developing LMD.