Characteristics and clinical outcome of BRCA germline mutation carriers with advanced breast cancer treated with PARP (poly ADP-ribose polymerase) inhibitors: A single institution experience.
Authors: Akkoc Mustafayev Fatma Nihan , Munsell Mark , Gutierrez-Barrera Angelica M. , Yam Clinton , Layman Rachel M. , Arun Banu 
Published: June 2023

10587 Background: About 5-10% of breast cancers (BC) are related to germline BRCA 1/2 pathogenic variants (PV). Several studies have demonstrated the effectiveness of PARP inhibitors (PARPi) in this population. However, BC patients with BRCA PVs remain a challenge to treat. In this report, we aim to characterize the clinical characteristics and outcome of a single institution cohort of advanced BC patients with a BRCA PV and who received PARPi therapy. Methods: Patients with BRCA 1/2 germline PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2022 as part of their treatment for metastatic or recurrent disease were included in the analysis. Variables included in this analysis included age at diagnosis, family history of BC and ovarian cancer, treatment details, tumor characteristics including histological type, receptor status and clinical outcome. Descriptive statistics, the Kaplan-Meier method, and The Cox proportional hazards regression model were used to report patient characteristics and outcomes. Progression free survival (PFS) was defined as the time from treatment initiation of PARPi to disease progression or death. Overall survival (OS) was defined as the time from treatment initiation of PARPi to death of any cause. Results: One hundred and seven patients were treated with PARPi. Median age at diagnosis was 38 years (23-73). Forty-eight (44.9%) and 59 (55.1%) patients had BRCA1 and BRCA2 mutations, respectively. Ninety-seven (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple negative BC. Nineteen (17.8%) patients were de novo metastatic BC (Stage IV). Sixty-two (57.9%) patients received one or more prior lines of chemotherapy before being treated with PARPi; 24 (22.4%) patients received prior platinum. In 91 patients evaluable for clinical response, the overall response rate (ORR) was 59.4% and the duration of response (DoR) was 7 months (2.1-96.2). In platinum-naïve patients ORR was 70.4% and DoR 7.4 months (2.1-96.2). Median PFS was 8.9 months (95% CI 6.3-10.3) and median OS 25.8 mo (95% CI 18.3-30.9). In univariate analysis, first-line PARPi use (p = 0.0274) and no previous use of platinum (p = 0.0121) were statistically significant for better PFS. Hormone receptor positive BC (p = 0.0105) was statistically significant for better OS. Conclusions: In this real-world single institution cohort of advanced BC patients with BRCA germline PVs who were treated with PARPi, the ORR and outcome of patients is similar to those reported in the previous clinical trials. Platinum naïve and patients who received PARPi as 1st line therapy had a better ORR. Further studies of predictive markers of response and resistance as well as sequencing with platinums are needed to optimize the use of PARPi in this patient population.