Leptomeningeal disease and breast cancer: the importance of tumor subtype.

Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. We aimed to characterize clinical features and outcomes of patients with LMD based on BC subtypes. We retrospectively reviewed records of 233 patients diagnosed with LMD from BC between 1997 and 2012. Survival was estimated by the Kaplan-Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Of 190 patients with BC subtype available, 67 (35 %) had hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative BC, 56 (29 %) had HER2+BC, and 67 (35 %) had triple-negative BC (TNBC). Median age at LMD diagnosis was 50 years. Median overall survival (OS) from LMD diagnosis was 4.4 months for HER2+BC (95 % CI 2.8, 6.9), 3.7 months (95 % CI 2.4, 6.0) for HR+/HER2-BC, and 2.2 months (95 % CI 1.5, 3.0) for TNBC (p = 0.0002). Older age was associated with worse outcome (p < 0.0001). Patients with HER2+BC and LMD were more likely to receive systemic therapy (ST) (p = 0.001). Use of intrathecal therapy (IT) (52 %) was similar (p = 0.35). Both IT (p < 0.0001) and ST (p < 0.0001) administration were associated with improved OS. After adjusting for age, IT, extracranial disease, and ST, patients with HER2+BC had better OS compared with HR+/HER2-BC (HR 1.72; 95 %CI 1.07-2.76) and TNBC (HR 3.30; 95 %CI 1.98-5.52). LMD carries a dismal prognosis. Modest survival differences by tumor subtype were seen. Patients with HER2+BC had the best outcome. There is an urgent need to develop effective treatment strategies.