ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
BRCA Genetic Testing and Treatment Patterns for Patients With HER2-Negative Early-Stage Breast Cancer in the US Community Setting
Provisionally accepted
Kathryn E. Mishkin1*
Yezhou Sun1
Ke Meng1Xiaoqing Xu2Qixin Li2Yu-Han Kao1Jagadeswara Rao Earla1Kim M. Hirshfield1Jaime A. Mejia1- 1Merck & Co Inc, Rahway, United States
- 2AstraZeneca, Gaithersburg, MD, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 (gBRCAm), and contemporary real-world data are needed regarding BRCAm testing patterns, BRCAm 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 BRCAm 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 BRCAm status. Results:Among 3741 patients with HER2-negative eBC, 51% and 56% were BRCAm tested in 2022 and 2023, respectively, >99% for germline BRCAm, 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. 35% with no BRCAm). 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 BRCAm tested, received adjuvant olaparib as monotherapy (6 patients) or in a combination regimen (12 patients). Conclusions:BRCAm 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 BRCAm testing for HR+/HER2-negative eBC, in addition to TNBC, and improving the timeline of BRCAm testing by implementing genetic testing before surgery to inform treatment decisions.
Keywords: adjuvant therapy, biomarker testing, BRCA, breast cancer, Endocrine therapy, Real-world study, Recurrence, targeted therapy
Received: 22 Oct 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Mishkin, Sun, Meng, Xu, Li, Kao, Earla, Hirshfield and Mejia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kathryn E. Mishkin
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.