Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases from 1985 to Today

Abstract Background Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment, GPA) for breast cancer patients with brain metastases (BCBM), based on cohort A (1985-2007, n=642), then updated it, reporting the impact of tumor subtype in cohort B (1993-2010, n=400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the three cohorts. Methods A multi-institutional (19) multi-national (3) retrospective database of 2473 breast cancer patients with newly-diagnosed brain metastases (BCBM) diagnosed from 1/1/2006-12/31/2017 was created and compared to prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated, such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively. Results Median survival (MS) for cohorts A, B and C improved over time [from 11, to 14 to 16 months, respectively (p Conclusion MS has improved modestly, but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free on-line calculator available at brainmetgpa.com). The Breast-GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest HER2-targeted therapies improve clinical outcomes in some patients with BCBM.