Abstract P2-08-21: Overall survival associated with BRCA or ATM mutation status in patients with metastatic triple-negative breast cancer: Findings from the PRIOR-2 study
Authors: Gboyega Adeboyeje, Maria Sierra, Amy Bartels, Michelle Field, Sumit Jhamb, Ami Buikema, Seongjung Joo
Journal: Cancer Research (2022)

Abstract Background: Many clinical guidelines recommend patients with metastatic triple-negative breast cancer (mTNBC) undergo mutational testing of genes involved in DNA damage repair response as a predictive marker of clinical benefit from recently approved targeted therapies. However, there is little known regarding the prognostic impact of BRCA1/2 or ATM mutation on the survival experience of mTNBC patients receiving contemporary routine care in the United States.Methods: In this retrospective cohort study, we identified patients aged ≥18 years with metastatic BC (≥2 BC diagnoses within 90 days and ≥1 diagnosis or ≥2 note mentions of metastatic disease) in Optum’s de-identified electronic health record (EHR) database (1/1/2013 - 6/30/2020; N=22.5M total lives). Index date was first diagnosis/note mention of metastatic disease; TN status was based on ER, PR and HER2 negative test results in the 1-year baseline through 90 days post-index. Patients were stratified by BRCA/ATM status and followed for up to 24 months from the start of treatment to assess overall survival (OS) using death information captured from the EHR and linked social security and obituary data. Differences in 2-year OS by BRCA/ATM status were evaluated using a Cox Proportional-Hazards model, adjusting for baseline demographics, comorbidities, clinical and prognostic factors.Results: Among 3,017 patients with mTNBC, 1,234 (40.9%) had evidence of being tested for BRCA/ATM: 394 (31.9%) had a BRCA/ATM mutation (POS), 487 (39.5%) were negative for a BRCA/ATM mutation (NEG), and 353 (28.6%) had unknown BRCA/ATM mutation status. Patients with a BRCA/ATM mutation had a mean age (SD) of 49.5 (12.9) years, while NEG patients had a mean age (SD) of 51.2 (12.1) years. Among POS patients, 22.1% had 2+ metastases at diagnosis, 11.4% had bone metastases, 5.6% had brain metastasis, 5.1% had liver metastasis, and 9.1% had lung metastasis. Among NEG patients, 18.5% had 2+ metastases at diagnosis, 9.4% had bone metastases, 5.7% had brain metastasis, 5.3% had liver metastasis, and 8.4% had lung metastasis. Of the 762 patients (338 POS; 424 NEG) with known stage at diagnosis, 40% of both POS and NEG patients presented at stage 3/4. Two-year OS rates were not significantly different by BRCA/ATM mutation status from start of treatment in the metastatic setting (POS: 79.3% vs NEG: 74.6%, p=0.30); unadjusted hazard ratio (HR) 1.28 (95% CI =0.81-2.03); adjusted HR 1.22 (95% CI 0.75-2.00). Conclusion: In this observational study of US patients with mTNBC, there was no statistically significant difference in 2-year OS rates between patients with or without BRCA/ATM mutation. OS at 2-years may have been overestimated in our sample due to the potential for unobserved death. Additional research is needed to evaluate the association between BRCA/ATM status and overall survival in different patient populations. Citation Format: Gboyega Adeboyeje, Maria Sierra, Amy Bartels, Michelle Field, Sumit Jhamb, Ami Buikema, Seongjung Joo. Overall survival associated with BRCA or ATM mutation status in patients with metastatic triple-negative breast cancer: Findings from the PRIOR-2 study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-21.