Leptomeningeal disease and breast cancer: Relationship of outcome and subtype.

Abstract

601 Background: Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. Outcome of leptomeningeal disease (LMD) across BC subtypes is not well documented. We aimed to characterize clinical features and outcomes of LMD based on BC subtypes. Methods: We retrospectively reviewed medical records of patients diagnosed with LMD from BC (1997 to 2012). All patients had BC. Cases of LMD were based on the presence of neoplastic cells on cerebrospinal fluid examination and/or evidence of LMD by imaging studies. Survival was estimated by the Kaplan-Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Results: 232 patients were included, 189 of them had available tumor subtype classified as: hormone receptor positive (HR+) BC N=67 (35.5%), human epidermal growth factor receptor 2 positive (HER2+) N=55 (29%), and 67 (35.5%) triple-negative BC (TNBC). Median age at diagnosis of LMD was 49.7 years. (Range 24-89). Median overall survival (OS) from LMD diagnosis across all subtypes was 3.1 months (95% CI, 2.5 to 3.7). Median OS correlated with BC subtype: 3.7 months (95% CI: 2.4, 6.0) in HR+, 4.0 months (95% CI: 2.6, 6.9) in HER2+, and 2.2 months (95% CI: 1.5, 3.0) in TNBC, (p=0.0002). There was an 11.4% chance a patient diagnosed with LMD would survive 1 year and the chance of surviving at least 3 years was 1.3%. When age was used as a continuous variable, older age was associated with worse outcome (p<0.0001). Patients with HER2+ BC and LMD were more likely to have received systemic therapy (ST) (70%), compared to HR+ (41%) and TNBC (41%) (p=0.002). 38% of patients with HER2+ BC received HER2 directed therapy. There was no difference in the use of intrathecal therapy (IT) (52%) across subtypes (p=0.3). Use of IT therapy (p<0.0001) and ST (p<0.0001) were both associated with improved age-adjusted OS. After adjusting for age, ST, there was no difference in OS between patients with HR+ and HER2+ BC (p =0.14), but a significant difference remained between TNBC and HER2+ BC (p < 0.0001). Conclusions: LMD carries a dismal prognosis. Our data shows that OS correlates with tumor subtype. Patients with TNBC had a significantly shorter OS compared to patients with HER2+ BC. New treatment strategies are needed.