Effect of breast cancer receptor subtypes and CSF cytology status on survival for patients with leptomeningeal disease.

2025 Background: Leptomeningeal disease (LMD) in metastatic breast cancer (MBC) carries a poor prognosis. Data on the effect of BC sub types and CSF cytology results on overall survival (OS) are lacking. This single institution retrospective study compares OS among MBC with LMD across BC sub types and CSF cytology results. Methods: This study included patients (pts) diagnosed with MBC LMD from Jan 2010 to Jan 2023. BC sub types were defined as (1) ER positive (+)/HER2 negative (-), HER2+, triple-negative BC (TNBC), (2) HER2 0 [immunohistochemistry (IHC) score 0], HER 2 low [ IHC 2+ with fluorescence in-situ hybridization negative OR IHC 1+], HER2+. ER and HER2 positivity were defined per ASCO/CAP criteria. CSF cytology sub types were CSF+ (for malignant cells), CSF-, and CSF not tested. Baseline characteristics were compared using Fisher’s Exact and Wilcoxon rank-sum tests. OS among sub types was evaluated using Kaplan-Meier analysis and compared using log rank test. For multivariate analysis, a step wise model selection was performed after inclusion of sub type of interest; and variables meeting entry (p<0.10) and staying criteria (p<0.05) were included in final Cox model. Results: Out of 219 patients screened, 69 pts were registered. Median OS and associated 95% confidence interval (CI) within BC sub types in analyses 1 and 2 and CSF sub type analysis are shown in the table. OS in analysis 1 was not significantly different by BC sub types. In multivariate analysis, TNBC sub type had significantly shorter OS than ER+/HER2- group [Hazard Ratio (HR) 2.64, 95% CI (1.23, 5.80) (p=0.04)] after adjusting for interval from MBC to LMD diagnosis and CSF cytology status. OS by BC sub types in analysis 2 was not significantly different in unadjusted and multivariate analyses. CSF- group had significantly better OS compared to CSF+ or CSF not tested group in unadjusted analysis (Table) and multivariate analysis [CSF+ vs CSF- HR 4.5 95% CI (1.75-12.11); CSF not tested vs CSF- HR 2.91 95% CI (1.45-6.26), overall p=0.002]. Conclusions: This single institution study on MBC pts with LMD showed that BC receptor sub types were significantly associated with OS when adjusted for the interval from MBC to LMD diagnosis and CSF cytology group. This study showed significantly improved OS among patients with negative CSF cytology compared to those with positive cytology or those not tested, indicating a novel prognostic value of CSF cytology (currently on diagnostic value) for MBC LMD. These findings will be further validated. [Table: see text]