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

TL;DR

This study examines BRCA genetic testing and treatment patterns for early-stage HER2-negative breast cancer patients in the US, finding suboptimal testing rates and highlighting areas for improvement.

Contribution

The study provides real-world data on BRCA testing patterns and treatment decisions for HER2-negative early-stage breast cancer patients in the US community setting.

Findings

BRCAm testing rates were 51% in 2022 and 56% in 2023 for HER2-negative early-stage breast cancer patients.

Only 3% of HR+/HER2-negative patients and 13% of triple-negative breast cancer patients tested positive for BRCA mutations.

Most patients with BRCA-mutated breast cancer underwent mastectomy compared to those without mutations.

Abstract

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.

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.

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. 32% 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).

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.

Figures