Abstract P2-08-16: Impact of germline <i>BRCA</i> mutation status on survival in women with metastatic triple negative breast cancer
Authors: K Larson, YY Wang, K Finke, AP O'Dea, Q Khan, L Nye, J Heldstab, AK Godwin, BF Kimler, P Sharma
Journal: Cancer Research (2019)

Abstract Background: 15-20% of patients with triple negative breast cancer (TNBC) harbor deleterious germline (g) BRCA1/2 mutations. Recent data suggests that in metastatic TNBC (mTNBC) gBRCA1/2 mutations are associated with response to PARP inhibitors (PARPi) and platinum chemotherapy. However, diagnosis of mTNBC is associated with short overall survival (OS) with no available biomarkers that can identify mTNBC patients with better prognosis. Aim: Utilizing data from a prospective registry, the objective of this study was to investigate whether presence of gBRCA1/2 mutation impacts overall survival for patients with mTNBC treated prior to clinical availability of PARPi. Methods: 643 patients with stage I-IV TNBC were enrolled in an IRB approved multisite prospective registry between 2011 to 2018. Clinical, demographic, and treatment information was collected and patients were followed for recurrence and survival. 100/643 patients had metastatic breast cancer (de novo stage IV disease or metastatic recurrence). OS (from the time of diagnosis of metastatic disease to death from any cause) was estimated according to the Kaplan-Meier method and compared among groups by log-rank test. Results: For the 100 mTNBC patients, the median age at diagnosis of metastatic disease was 55 years, 17% were African American, 20% had novo stage IV and 80% had relapsed disease. 84% had visceral disease, 12% had bone-only disease, and 4% had lymph node only disease. Metastatic treatment: 87% received chemotherapy, 7% received radiation only without chemotherapy and 6% did not receive any treatment. No patients received treatment with PARP inhibitor. Among de-novo stage IV patients, 35% (7/20) had breast surgery for removal of primary tumor during their course of metastatic treatment. For all 100 patients, 12% (n=12) had gBRCA mutation; 72% (n=72) had no gBRCA mutation; and 16% (n=16) had unknown BRCA mutation status. When compared with non-carriers, gBRCA carriers were younger at time of metastatic diagnosis (median age 49 vs. 57 years, p=0.02). There was no difference in prevalence of visceral disease, de-novo stage IV disease or median lines of metastatic chemotherapy among gBRCA carriers and non-carriers. At a median follow up of 31 months, median OS for all patients is 21 months (95% CI 13-23 months). Median OS is 18 months (95% CI 15-27 months) for non-carriers and has not yet been reached for gBRCA mutation carriers (p=0.023). 3-year estimated OS is 63% in gBRCA carriers compared to 28% in non-carriers (p=0.02). On multivariate Cox regression analysis, gBRCA carrier status was associated with reduced risk of death (HR=0.33; 95%CI [0.23-0.91], p=0.033) Conclusions: gBRCA mutation associated mTNBC patients have a clinically significant improved OS at 3 years compared to mTNBC patients without BRCA mutations (3-year OS of 63% vs 28%). Further research is needed to understand tumor and host biological reasons for this observation. Outcomes of gBRCA mutation associated mTNBC are likely to be further improved with availability of PARPi. Given that patients with gBRCA mutation are at risk for second breast/ovarian cancers, these findings also underscore need for further research regarding the role of prophylactic surgeries mTNBC with gBRCA mutation. Citation Format: Larson K, Wang YY, Finke K, O'Dea AP, Khan Q, Nye L, Heldstab J, Godwin AK, Kimler BF, Sharma P. Impact of germline BRCA mutation status on survival in women with metastatic triple 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 P2-08-16.