Metastatic breast cancer (MBC) behavior differs depending on the molecular subtype based on hormone receptors (HR) and HER2 statuses. We aimed at evaluating the kinetics of central nervous system metastases (CNSM) occurrence, and the prognosis after CNSM, according to the molecular subtype.
Retrospective analysis of 16703 MBC patients from the French Epidemiological Strategy and Medical Economics (ESME) database involving 18 specialized cancer centers (NCT03275311) (2008-2014 database). The time between stage IV and CNSM diagnosis (CNSM-free survival CNSMFS) and between CNSM diagnosis and death from any cause (overall survival OS) were estimated with the Kaplan-Meier method and compared with the log-rank test.
Median follow-up was 42.8 months. Among the selected patients, 64.1% of patients had HR+/HER2-, 11.0% HER2+/HR+, 7.5% HER2+/HR- and 17.4% triple negative (TN, HR-/HER2-) MBC. Median age at MBC diagnosis was 61.2. 4118 patients (24.6%) were diagnosed with CNSM at initial diagnosis of primary tumor or during their MBC follow-up: 18.7%, 34.9%, 49.2% and 38.0% of patients with HR+/HER2-, HER2+/HR+, HER2+/HR- and TN tumors, respectively. Median age at CNSM diagnosis was 58.1 overall, 54.1 for TN patients and 59.9 for HER2+ patients (p < 0.0001). 1200 patients (7.2%) had CNSM at the time of stage IV diagnosis, while 2918 developed CNSM during the course of MBC, with a median CNSMFS of 17.0 months (95% CI 16.5-17.9). The molecular subtype was independently associated with CNSMFS: HER2-/HR+ NE (95%CI 91.1NE), HER2+/HR+ 61.7 (95%CI 51.7-74.1), HER2+/HR- 24.9 (95%CI 22.7-28.9) and TN 29.9 months (95%CI 27.0-33.1) (p < 0.001). With a 30 months median follow-up, median OS after CNSM diagnosis was 7.9 months (95% CI 7.2-8.4): 7.1 months for HR+/HER2-, 18.9 months for HER2+/HR+, 13.1 months for HER2+/HR- and 4.4 months for TN (p < 0.0001). These differences were significant when assessed in multivariate analysis (p < 0.0001 for HER2+/HR+, HER2+/HR- and TN tumors compared with HER2/ HR+ tumors).
We found that the breast cancer molecular subtype strongly impacts the occurrence, kinetics and prognosis of CNSM in MBC patients.
Clinical trial identification
Legal entity responsible for the study
Pierre Fabre, Pfizer, AstraZeneca and MSD.
All authors have declared no conflicts of interest.