Intracranial progression-free survival correlates with overall survival and varies by tumor subtype in patients with...

Brain metastases in patients with breast cancer (BCBM) are common. While the Breast Graded Prognostic Assessment (Breast GPA) predicts overall survival (OS), its ability to predict intracranial progression-free survival (icPFS) has not been established.

We conducted a retrospective, multi-institutional cohort study to evaluate the association between Breast GPA and icPFS among BCBM patients treated initially with stereotactic radiosurgery (SRS) or whole-brain radiation therapy (WBRT). icPFS was defined as the time from initial local BCBM treatment to the first local salvage treatment or death.

Among 2263 patients, 49% received SRS and 51% WBRT. Subtypes included hormone receptor (HR)+/HER2- (31%), HR+/HER2+ (21%), HR-/HER2+ (17%), and triple-negative breast cancer (TNBC) (24%). The median icPFS ranged from 6 months (TNBC) to 12 months (HR+/HER2+). By Breast GPA, the median icPFS ranged from 5 months (GPA 0.0-1.0) to 13 months (GPA 3.5-4.0), and the median OS ranged from 6 to 37 months, respectively. The bias-corrected c-index for Breast GPA was 0.606 for icPFS and 0.648 for OS. icPFS and OS were strongly correlated (r = 0.783; 95% confidence interval, 0.739-0.836). In multivariable analysis, breast cancer subtype, number of BCBM, and Karnofsky Performance Status were the strongest icPFS predictors.

The Breast GPA predicts OS and icPFS in BCBM patients, providing valuable benchmarks for clinical trial design. These data establish historical controls for icPFS by subtype and Breast GPA and may guide systemic therapy prioritization in patients at greatest risk of early intracranial progression.