A 25-Year Snapshot of Survival With Metastatic Breast Cancer and Brain Metastases

A retrospective study in Breast Cancer Research has illustrated survival trends by breast cancer subtype over 2 decades and pinpointed predictors of survival among patients with metastatic breast cancer and brain metastases (BM), underscoring the critical need for subtype-specific treatment and management strategies.¹

The study examined a cohort of 507 patients diagnosed with metastatic breast cancer and BM between 1997 and 2024 at the University of California San Francisco. The median real-world overall survival (rwOS) of this cohort from BM diagnosis to death was nearly 2 years (21.6 months), with key significant differences observed between disease subtypes (P <.001). Patients with HER2-positive (HER2+) BM had notably prolonged survival (median rwOS, 31.0 months); comparatively, those with hormone-receptor-positive (HR+), HER2-negative (HER2–) breast cancer and triple-negative breast cancer (TNBC) had respective rwOS of 19.6 months and 12.8 months.

Regarding temporal trends over the 27-year period, patients with HER2+ disease who were diagnosed with BM more recently (after 2014) lived longer compared with those diagnosed earlier (median rwOS, 41.2 vs 26.2 months; P =.002). A similar trend followed in patients with TNBC (median rwOS, 14.9 vs 7.0 months; P =.020). Importantly, the same survival improvement was not observed in patients with HR+/HER2– disease (median rwOS, 16.5 vs 21.6 months; P =.089). This lack of meaningful improvement indicates a potential unmet need for better systemic treatments in patients with this subtype, according to the authors.

“Our results suggest a potential area of unmet clinical need for new systemic treatment strategies for patients with HR+/HER2– [metastatic brain cancer] with BMs,” said authors Krasnow et al in the publication.¹

In terms of prognostic risk factors, HER2 positivity, BM surgical resection, and diagnosis after 2014 were associated with longer survival (HR range, 0.64–0.77), while TNBC, having 6 to 10 BMs at baseline, extracranial metastatic breast cancer, and development of leptomeningeal disease were associated with shorter survival (HR range, 1.34–1.66).

Cohort Characteristics and Treatments

In the full cohort, the median age at metastatic breast cancer diagnosis was 53 years (range, 25–92). The median time from breast cancer diagnosis to BM diagnosis was 8.1 months; notably, patients with TNBC experienced the shortest time (2.8 months), followed by patients with HER2+ (8.3 months) and patients with HR+/HER2– (16.2 months). More than 75% of patients had extracranial disease at BM diagnosis. A vast majority of patients received radiation treatment for BM (95.2%), and about a third of patients (30%) underwent surgical resection.

In response to BM diagnosis, many patients were treated with central nervous system (CNS)-penetrant therapies. Specifically, 19.6% were treated with HER2-targeted tyrosine kinase inhibitors, 2.8% with abemaciclib (Verzenio), 8.7% with trastuzumab emtansine (Kadcyla; T-DM1), 10.3% with trastuzumab deruxtecan (Enhertu; T-DXd), 5.9% with sacituzumab govitecan (Trodelvy), and 6.9% with checkpoint inhibitors.

Clinical Implications

Although the study’s retrospective, single-center nature may limit generalizability of the findings, the survival gains made since the turn of the century, as evidenced by this study, likely partially reflect the increased availability and improvements of novel CNS-penetrant therapies. However, the authors noted that “while many novel therapeutics for [metastatic breast cancer] have been shown to have intracranial efficacy, it remains possible that the survival benefit is due to improved treatment of extracranial disease, rather than improved CNS disease control.”¹

These real-world outcomes reinforce the importance of continued clinical evaluation of patients with metastatic breast cancer and BM, especially given the subtype-dependent variation in time to BM. With new insights into prognostic risk factors associated with survival, this new knowledge may help guide such efforts.

REFERENCE

1. Krasnow NA, Jayaraj M, Salans M, et al. Evaluating survival trends over time in patients with metastatic breast cancer and brain metastases: a single center retrospective cohort study. Breast Cancer Res. 2025;27(1):191-191. doi:10.1186/s13058-025-02121-7