Approximately 20–30% of patients with metastatic breast cancer (MBC) develop brain metastases (BM) over the course of their disease. It is critical to better understand risk factors and survival outcomes in these patients, including those treated in the modern treatment era.

We identified patients with MBC and BM diagnosed between 1997 and 2024 at our institution. Review of medical records was completed to identify key demographic, clinical, and survival characteristics.

We identified 507 patients with MBC and BMs with the following subtypes: HR+/HER2- (n = 184, 36.3%), HER2+ (n = 197, 38.9%), and triple negative breast cancer (TNBC; n = 126, 24.9%). Median real-world overall survival (rwOS) from the diagnosis of first BM to death was 21.6 months with the longest median rwOS in patients with HER2+ disease (31.0 months) vs. patients with HR+/HER2- (19.6 months) or TNBC (12.8 months) (p < 0.001). By date of BM diagnosis 1997–2014 vs. 2015–2024 (divided by ~ 50% of patients in each time period), patients with HER2+ and TNBC lived longer in the more modern cohort compared to prior years (HER2+: 41.2 vs. 26.2 months, p = 0.002; TNBC: 14.9 vs. 7.0 p = 0.020). There was no statistically significant difference for patients with HR+/HER2- disease (16.5 vs. 21.6, p = 0.089). On multivariable analysis, HER2+ disease (HR 0.64, 95% CI 0.50–0.81, p < 0.001), BM surgical resection (HR 0.67, 95% CI 0.51–0.87, p = 0.002), and BM diagnosis after 2014 (HR 0.77, CI 0.63–0.95, p = 0.015) were associated with longer survival. TNBC (HR 1.46, CI 1.12–1.89, p = 0.004), having 6–10 BMs at baseline (HR 1.66, CI 1.14–2.42, p = 0.009), extracranial MBC (HR 1.34 CI 1.02–1.76, p = 0.034) and development of leptomeningeal disease (HR 1.41, CI 1.11–1.80, p = 0.005) were associated with shorter survival.

In a cohort of > 500 patients with MBC BMs spanning > 25 years, median rwOS from the diagnosis of first BM was almost two years. Favorable factors included HER2+ disease, BM surgical resection, and diagnosis after 2014. Poor prognostic factors included TNBC, having 6–10 BMs, extracranial MBC, and development of LMD. Patients with HER2+ and TN MBC with BM had improved rwOS in a more modern cohort; this was not seen for HR+/HER2- patients, representing an area of ongoing unmet clinical need.