Clinical Outcomes, Treatment Patterns, and Health Resource Utilization Among Metastatic Breast Cancer Patients with Germline BRCA1/2 Mutation: A Real-World Retrospective Study

Abstract

Introduction: With evolving treatment guidelines for germline BRCA1/2 mutation (gBRCAm) in breast cancer, we present the latest gBRCA testing rates among metastatic breast cancer (mBC) patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) or triple-negative breast cancer (TNBC). Among these patients with gBRCAm, we analyzed clinical outcomes, treatment patterns, and health resource utilization (HRU).

Methods: The Flatiron Health electronic health record database was used to assess gBRCA testing rates in a real-world retrospective analysis of US patients at least 18 years old with HR+/HER2- or TNBC, and with mBC diagnosed from January 2011 to February 2018. Outcomes were compared between gBRCAm patients with HR+/HER2- vs TNBC, adjusting for imbalances utilizing inverse probability treatment weighting; effects of HR+/HER2- vs TNBC on overall survival (OS) were assessed, antineoplastic treatments summarized, and HRU analyzed using t tests.

Results: The study included 12,021 mBC patients (HR+/HER2-, 10,291; TNBC, 1730). Results for gBRCA testing were available for 2005 (16.7%) patients (HR+/HER2-, 1587; TNBC, 418). A total of 229 (1.9%) patients (HR+/HER2-, 165; TNBC, 64) had gBRCAm. Significantly worse OS in gBRCAm mBC was observed in TNBC vs HR+/HER2- [hazard ratio (95% confidence interval), 0.45 (0.27-0.74); p = 0.002]. Estimated median and 4-year OS rates for gBRCAm mBC patients with either HR+/HER2- or TNBC were 38.0 months, 23.4 months and 35.6%, 21.2% respectively. The most common first-line treatment post diagnosis for gBRCAm HR+/HER2- was letrozole (8%) vs capecitabine (14%) for gBRCAm TNBC. The number of HRU treatment visits per patient per year was significantly (p < 0.05) higher among gBRCAm mBC patients with TNBC vs HR+/HER2-.

Conclusion: Among HER2- mBC patients, gBRCA testing rates are low. Among gBRCAm HER2- mBC patients, the poor OS and HRU burden observed, especially in patients with TNBC, demonstrate an unmet need for more efficacious, targeted, and less HRU-intensive treatment options.

Funding: Pfizer.

Keywords: Electronic health records; Germline BRCA mutation; Metastatic breast cancer.