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 (gBRCAm). Real-world data examining survival for patients with gBRCAm mBC, overall and separated into gBRCA1m and gBRCA2m, compared to gBRCA wild type (wt) mBC, can help to clarify the prognostic outlook associated with the gBRCA 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 gBRCA1m, gBRCA2m, or gBRCAwt disease. Those who did not receive the genetic testing or who had equivocal results were classified as gBRCA 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 gBRCA1m and gBRCA2m, and between overall gBRCAm and gBRCAwt.

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. gBRCA status was known for 1,852 (22.9%) of patients, of whom 89 (4.8%) had gBRCA1m, 152 (8.2%) had gBRCA2m, and 8 (0.4%) had both gBRCA mutations. Patients with known gBRCA status were younger, with mean ages of 52 years for gBRCAm, 55 years for gBRCAwt, and 67 years for gBRCA unknown. Hormone receptor positive disease was less common among those with known gBRCA status (71.9%, 77.2%, and 83.6% for gBRCAm, gBRCAwt, and gBRCA unknown, respectively). Median (95% CI) OS from mBC diagnosis was 22 (14 - 26) months for gBRCA1m and 30 (27 - 37) months for gBRCA2m (p = 0.01), though numbers were quite small by the median timepoint. Overall gBRCAm disease was associated with median survival of 28 (25 - 32) months, compared to 32 (30 - 35) months for gBRCAwt (p = 0.07); survival was similar between groups for the first 24 months but declined thereafter in the gBRCAm 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 gBRCA 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 gBRCA1m compared to gBRCA2m disease and may be reduced in gBRCAm mBC overall. Effective treatments targeted for the gBRCAm 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.