Clinical and molecular features of resected breast cancer brain metastases: a single center retrospective cohort study.

To characterize clinical and molecular characteristics and prognosis among patients with metastatic breast cancer (MBC) who undergo brain metastasis (BM) resection. We retrospectively identified patients with MBC who underwent BM resection from 2006 to 2024 at a single center. Chart abstraction was utilized to identify key demographic, treatment, and outcome data. Median real-world overall survival (mrwOS) was estimated with the Kaplan-Meier method; the Cox proportional hazards model evaluated factors associated with mrwOS. 107 patients were identified with the following MBC subtypes: hormone receptor-positive (HR+), HER2-negative (HER2-) (n = 26, 24.3%), HER2+ (n = 45, 42.1%), and triple-negative (TNBC; n = 36, 33.6%). At time of initial BM surgical resection, 55 patients (51.4%) had CNS-only disease and 63 patients (58.9%) had a single BM. Most patients received systemic therapy after BM resection (n = 83/95 with available systemic therapy records, 87.4%) and postoperative radiation (n = 92/103 with available post-operative radiation records, 89.3%). Among patients with available BM receptor status (n = 92), 25 (27.2%) had receptor discordance between BM and peripheral tissue testing, mostly loss of BM HR-positivity (n = 20/92, 21.7%). Among patients with available BM NGS testing (n = 40), the most common pathogenic alterations were TP53 mutation (n = 28, 70.0%), ERBB2 amplification (n = 15, 37.5%), and PIK3CA mutation (n = 9, 22.5%); 31 patients (77.5%) had therapeutically targetable mutations. mrwOS from BM resection was longer for patients with HR+/HER2- and HER2+ MBC vs. TNBC (40.3 and 37.8 months vs. 12.6 months, p = 0.04 and p = 0.02 respectively). On multivariate analysis, receipt of systemic therapy (HR 0.09, CI 0.04-0.21, p < 0.01) and stereotactic radiosurgery (SRS) (HR 0.41, CI 0.18-0.97, p = 0.04) post-operatively were associated with longer mrwOS. Extracranial disease at time of resection (HR 4.60, CI 2.52-8.39, p < 0.01) and development of leptomeningeal disease (LMD) (HR 6.08, CI 3.00-12.31, p < 0.01) were associated with shorter mrwOS. Survival after BM resection was ~3 years in patients with HR+/HER2- and HER2+ MBC and ~1 year in patients with TNBC. Extracranial disease at time of BM resection and development of LMD were associated with worse prognosis. Loss of HR-positivity and targetable mutations were present in ~22% and ~75% of resected BMs, respectively, supporting the utility of molecular analysis of resected BMs to guide management.