BRCA genetic testing and treatment patterns for patients with HER2-negative early-stage breast cancer in the US community setting

Background Adjuvant olaparib has been approved in the US since 2022 for patients with high-risk HER2-negative early-stage breast cancer (eBC) with germline mutation in BRCA1 or BRCA2 (g BRCA m), and contemporary real-world data are needed regarding BRCA m testing patterns, BRCA m prevalence, and therapy selection for HER2-negative eBC in the US. Methods This retrospective cohort study used a longitudinal, real-world dataset from US community healthcare systems to describe characteristics and BRCA m testing of adults with initial diagnosis from 1-Jan-2022 to 22-Jan-2024 of clinical stage I-III HER2-negative BC. Patients with unknown hormone receptor (HR) status, enrolled in a clinical trial, or with lobular carcinoma in situ or other primary cancer were excluded. Subsequent therapy was described by BRCA m status. Results Among 3741 patients with HER2-negative eBC, 51% and 56% were BRCA m tested in 2022 and 2023, respectively, 99% for germline BRCA m, and including 70% of 509 patients with triple-negative breast cancer (TNBC) and 50% of 3232 patients with HR+/HER2-negative eBC. Of 1985 patients tested before a metastatic diagnosis, testing was conducted for 2% before initial diagnosis, for 77% at/before surgery, and for 21% after definitive surgery; 96 (5%) had BRCA -mutated eBC, including 51 of 1630 (3%) with HR+/HER2-negative eBC and 45 of 355 (13%) with TNBC. With median follow-up of 20.2 months, 1922 patients (97%) underwent surgery, with greater proportion of patients with BRCA -mutated eBC undergoing mastectomy (83% vs. 32% with no BRCA m). Most patients (90%) received systemic therapy: 8% neoadjuvant-only, 65% adjuvant-only, and 18% both. Of 49 patients with BRCA -mutated HR+ eBC who had definitive surgery, 36 (73%) received adjuvant therapy, most commonly endocrine therapy-only (20/36, 59%). Of 44 patients with BRCA -mutated TNBC, 20 (45%) received adjuvant therapy, most commonly immunotherapy (11/20, 55%). Eighteen patients, all BRCA m tested, received adjuvant olaparib as monotherapy (6 patients) or in a combination regimen (12 patients). Conclusions BRCA m testing rates in the US remain suboptimal relative to practice guideline recommendations and availability of adjuvant targeted therapy for HER2-negative eBC. Particular areas of unmet need include BRCA m testing for HR+/HER2-negative eBC, in addition to TNBC, and improving the timeline of BRCA m testing by implementing genetic testing before surgery to inform treatment decisions.