Background: Brain metastases (BM) are an increasingly common consequence of breast cancer (BC). Knowledge of the microenvironment in primary BC and its impact on prognosis is evolving. A similar understanding of the microenvironment of BC metastases is lacking, particularly for the brain, where unique immune regulation governs stroma composition. Such features of the peri-tumoral landscape, i.e. high immune infiltrate and low hemorrhage, offer prognostic value in BM from melanoma. This study reports on 4 biomarkers, gliosis (glio), immune infiltrate (immune), hemorrhage (hem) and necrosis (nec), and their prognostic significance in BCBM. Methods: A biobank of 203 patients (pts) who underwent craniotomy between 1989-2013 was created across 4 sites. Glio, immune, and hem (grouped 0 v 1-3) and nec (0-2 v 3) were scored via H&E stain (0-3). Overall survival (OS (years)) from craniotomy was estimated using the Kaplan-Meier method; log-rank tests compared OS. Cox proportional hazards regression was used to evaluate prognostic value of the 4 biomarkers. Results: Mean age at primary BC diagnosis was 48 years (range 26-77). BCBM subtype (n = 158) was 36% HER2+, 26% HR+/HER2-, 38% HR-/HER2- (TN). Across all samples, expression was 82% glio, 45% immune, 82% hem, and 13% nec. Subtype differences were seen for nec (higher in TN, p < 0.01). Across all pts, expression of glio, immune, and hem was associated with improved OS (years): 1.08 v 0.62 (p = 0.03), 1.31 v 0.93 (p = 0.03), 1.07 v 0.92 (p = 0.1), respectively. Nec was associated with inferior OS: 0.38 v 1.12 (p = 0.01). The association with improved OS was maintained for glio in TN (p = 0.02), and immune (p = 0.001) and hem (p = 0.07) in HER2+. In a multivariable model for OS, adding the 4 biomarkers to traditional clinical variables (age, race, subtype) significantly improved the model fit (p < 0.001). Conclusions: Nec is a poor prognostic finding in BCBM across all subtypes. Glio confers superior prognosis in TN, while immune and hem correlate with superior prognosis in HER2+. A deeper understanding of the rich BCBM microenvironment both refines prognostic considerations for this pt population and may lead to future investigations of targeted immunotherapies in select subtypes of BCBM.