Abstract PD1-13: Somatic BRCA mutation detection by circulating tumor DNA analysis in patients with metastatic breast cancer: Incidence and association with tumor genotyping results, germline BRCA mutation status, and clinical outcomes
Authors: N Vidula, SJ Isakoff, A Niemierko, G Malvarosa, H Park, E Abraham, L Spring, J Peppercorn, B Moy, LW Ellisen, D Juric, A Bardia
Journal: Cancer Research (2018)

Abstract Introduction: BRCA mutations may impact patient outcomes, as well as chemotherapy response in patients with breast cancer (BC). While germline BRCA mutations have been well-studied, the incidence and clinical impact of somatic BRCA mutations have not been well-described. We evaluated the presence of BRCA mutations, and the association between somatic BRCA mutations with clinical outcomes in patients with metastatic breast cancer (MBC). Methods: We identified patients with MBC who underwent ctDNA testing by Guardant360 at our institution before the start of a new therapy. From this subset of patients, we subsequently identified those patients with circulating tumor DNA (ctDNA) BRCA 1 or 2 mutations. We conducted a retrospective review of medical and pathology records to identify tumor subtype, germline BRCA testing results, and tissue genotyping results based on institutional Snapshot-NGS genotyping assay. In addition, we conducted a multivariate analysis to evaluate the hazard ratio (HR) for the association between ctDNA BRCA mutation and progression free survival (PFS) adjusting for age, number of prior therapies, and type of therapy. Results Among patients with MBC (N = 178), 27 (15.2%) had BRCA alterations detected by ctDNA analysis. Among patients with ctDNA BRCA alterations, the median age at metastatic diagnosis was 53; 16/24 (66.6%) had hormone receptor (HR)+/HER2- BC, 5/24 (20.8%) had triple negative (TN) BC, 2/24 (8.3%) had HR-/HER2+ BC, and 1/24 (4.2%) had HR+/HER2+ BC. Of patients with ctDNA BRCA mutations, only a minority (16.7%) had BRCA alterations detected by genotyping of archival tumor, and only 1 (3.7%) had a germline BRCA mutation (BRCA 1). In multivariate analysis, patients with BRCA mutant tumors, had similar median PFS as compared to non-BRCA mutant breast cancer (HR: 1.17; p = 0.58). Overall survival analysis and impact of BRCA mutations on response to therapy, particularly DNA damaging agents, will be presented at the meeting. Conclusions: BRCA mutations by ctDNA are detectable in a significant proportion of MBC patients. Most BRCA mutations detected by ctDNA were not identified by genotyping of archival tissue, and were not associated with germline BRCA mutations, suggesting that somatic BRCA mutations may be detected by sensitive blood-based genotyping assays in patients who are not known BRCA carriers. The therapeutic impact of DNA damaging agents and PARP inhibitors in MBC patients with somatic BRCA alterations is not known and warrants additional research. Citation Format: Vidula N, Isakoff SJ, Niemierko A, Malvarosa G, Park H, Abraham E, Spring L, Peppercorn J, Moy B, Ellisen LW, Juric D, Bardia A. Somatic BRCA mutation detection by circulating tumor DNA analysis in patients with metastatic breast cancer: Incidence and association with tumor genotyping results, germline BRCA mutation status, and clinical outcomes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-13.