Abstract P1-09-13: A real world evidence study of BRCA mutations and survival in HER2-negative breast cancer

Background: Limited data exist on the natural history (treated with standard of care) of metastatic breast cancer (mBC) characterized by germline breast cancer susceptibility gene mutations (g BRCA m). Real-world data examining survival for patients with g BRCA m mBC, overall and separated into g BRCA1m and g BRCA2m , compared to g BRCA wild type (wt) mBC, can help to clarify the prognostic outlook associated with the g BRCA mutation. Methods: Adults with human epidermal growth factor receptor 2 negative (HER2-) mBC diagnosed from January 2013 – August 2017 were retrospectively selected from the Flatiron Health Oncology electronic medical record database. Patients were classified as having g BRCA1 m, g BRCA2 m, or g BRCA wt disease. Those who did not receive the genetic testing or who had equivocal results were classified as g BRCA unknown. Overall survival (OS) was calculated from first diagnosis of mBC, as well as from the start of first- and second-line therapy for metastatic disease. Lines of therapy included both hormonal and systemic therapies. Kaplan-Meier analyses provided median OS with 95% confidence interval (CI). Unadjusted log-rank tests compared OS between g BRCA1 m and g BRCA2 m, and between overall g BRCA m and g BRCA wt. Results: Of 8,080 patients selected, mean age at first mBC diagnosis was 64 years, 98.7% were female, and 82.0% had evidence of hormone receptor positive disease. g BRCA status was known for 1,852 (22.9%) of patients, of whom 89 (4.8%) had g BRCA1 m, 152 (8.2%) had g BRCA2 m, and 8 (0.4%) had both g BRCA mutations. Patients with known g BRCA status were younger, with mean ages of 52 years for g BRCA m, 55 years for g BRCA wt, and 67 years for g BRCA unknown. Hormone receptor positive disease was less common among those with known g BRCA status (71.9%, 77.2%, and 83.6% for g BRCA m, g BRCA wt, and g BRCA unknown, respectively). Median (95% CI) OS from mBC diagnosis was 22 (14 - 26) months for g BRCA1 m and 30 (27 - 37) months for g BRCA2 m (p = 0.01), though numbers were quite small by the median timepoint. Overall g BRCA m disease was associated with median survival of 28 (25 - 32) months, compared to 32 (30 - 35) months for g BRCA wt (p = 0.07); survival was similar between groups for the first 24 months but declined thereafter in the g BRCA m group. Similar patterns were observed for OS after the start of first- and second-line therapy, although no comparisons were significant. Further analyses will present adjusted results and comparisons with outcomes for the patients with g BRCA unknown. Conclusions: This real-world study of patients receiving care in largely community oncology clinics suggests that survival after diagnosis of mBC is reduced in patients with g BRCA1 m compared to g BRCA2 m disease and may be reduced in g BRCA m mBC overall. Effective treatments targeted for the g BRCA m subtypes of mBC appear to be needed. Citation Format: Dalvi T, McLaurin K, Briceno J, Nordstrom B, Bennett J, Hettle R, Murphy B, Collins J, McCutcheon S. A real world evidence study of BRCA mutations and survival in HER2-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-13.