Factors associated with developing and surviving brain metastases in patients with breast cancer: a multi-center...

Patients with breast cancer and brain metastasis (BCBM) have poor survival outcomes. We aim to explore predictors of survival in patients with BCBM including the Breast Graded Prognostic Assessment -GPA tool and its variables and review the impact of emerging targeted therapies.

The Cleveland Clinic database was retrospectively reviewed to identify patients diagnosed with BCBM between 2010 and 2020 at multiple treatment centers in Ohio and Florida. Data on demographic, clinical, and treatment variables were collected, including BC surgery, radiotherapy, chemotherapy, endocrine therapy, HER2-targeted therapy, immunotherapy, PARP inhibitors, CDK4/6 inhibitors, tyrosine kinase inhibitors (TKIs), BM characteristics (number, size, location), extracranial metastasis (ECM), and BM treatments. The Kaplan-Meier method was used to calculate median overall survival (mOS), and univariate and multivariate Cox regression models were adopted to identify significant survival predictors.

N = 318 evaluable patients with BCBM were included. Patients were aged 46-60 years (42.5%), female (99.7%), of white race (79.6%), and non-Hispanic (97.2%). Among BC subtypes, the triple positive subgroup had the longest mOS, while the triple negative subgroup had the shortest. Having one or less ECM was linked to longer survival compared to ≥ 2 ECM. Patients receiving HER2-targeted therapy, PARP inhibitors, and TKIs had significantly longer mOS than those who did not receive targeted agents. Additionally, patients who underwent BM surgery had significantly longer mOS. Patients treated with Stereotactic Radiosurgery (SRS) such gamma knife radiosurgery had the longest mOS among the radiotherapy subgroups.

BCBM is a heterogeneous population with variable outcomes. This analysis suggests that several factors influence the development and outcome after BCBM with HR+/HER2- subgroup having the longest median time to develop BM compared to other subgroups. Survival after BCBM is impacted by age, performance status and overall disease burden, as well as the use of novel targeted therapies suggesting the feasibility to overcome the historical blood brain barrier to systemic treatment benefit from chemotherapy. Brain surgery and Radiation modalities also play an important role in improving long term outcome. These results support updating current prognostic models, such as the Breast-GPA, by integrating treatment exposures, shifting from static baseline scores to dynamic, treatment-informed prognostication.