Changing recognition of breast cancer–related leptomeningeal disease and response to therapy: A retrospective single institution review.

Abstract

2027 Background: Breast cancer related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of breast cancer patients with overall survival (OS) measured in weeks without treatment. As new treatments prolong survival with breast cancer, the risk of developing BC-LMD may be increasing. We hypothesized that the rate of BC-LMD diagnosis increased significantly with time. We also predicted that OS with BC-LMD had changed with time and in relationship to molecular subtype and treatment following BC-LMD diagnosis. Methods: With approval of the local Scientific Research Committee and IRB, we conducted a retrospective analysis of medical records for patients treated or diagnosed with breast cancer at MCC from 2011-2020. Patient demographics, tumor characteristics, treatments, and outcomes were collected. Kaplan Meier survival curves were used to determine median overall survival (OS), progression of disease, and differences by molecular subtype. Univariate and multivariate analyses were used to determine characteristics of primary tumors and treatments which affected OS. Results: Of the 133 cases identified, significantly more were diagnosed between 2016-2020 than 2011-2015 (p < 0.01). Significant increases were seen in HER2+ and TNBC patients (p < 0.05) but not for ER/PR positive (HR+) disease (p = 0.058). HER2+ LMD associated with longest overall survival (OS; 7mths) followed by HR+ disease (3mths) and TNBC with the shortest OS (2mths). Systemic metastases preceded BC-LMD diagnosis in 72% of cases and CNS metastases in 85% of cases. HER2+ disease also conferred increased survival after CNS metastases were diagnosed until progression to LMD (8mth vs 2mth for HR+ and 1mth for TNBC LMD; p < 0.05). Positive impact on survival by HER2 targeted therapies may account for improved OS in this population. Other factors which increased OS generally were: WBRT, continuation of systemic therapy, delivery of intrathecal chemotherapy, and participation in clinical trials. Having TNBC and decision to defer treatment were associated with reduced OS. Conclusions: This study highlights the importance of identifying patients with BC-LMD early and with the intention to treat. Prospective clinical trials and population-based studies are needed to advance treatment of BC-LMD.