Abstract PS2-02-03: Real-world treatment patterns in 1954 US patients with HER2-negative early breast cancer and germline BRCA mutations (2021-2025)

Abstract Background: In 2022, the US FDA approved adjuvant olaparib for patients (pts) with germline pathogenic/likely pathogenic mutations in BRCA1 and/or BRCA2 (gBRCAm) and high-risk HER2-negative (HER2−) early breast cancer (eBC), based on significant survival improvements with olaparib vs placebo in OlympiA. In clinical practice, select pts with high-risk HER2− eBC may also receive CDK4/6 inhibitors (CDK4/6i) or immuno-oncology (IO) therapies; however, data are limited on treatment preference and sequencing in these pts. We describe real-world treatment patterns in US pts with gBRCAm HER2− eBC. Methods: Data from pts aged ≥18 years diagnosed with HER2− eBC (stage I-III) between January 1, 2021, and January 31, 2025, and with gBRCAm, were captured in the deidentified, electronic health record-derived Flatiron Health Research Database. Demographics, clinical characteristics, and treatment patterns were described across tumor subtypes (hormone receptor-positive HR+ or triple-negative eBC TNBC). Pts with high-risk eBC were defined using criteria adapted from OlympiA (Tutt et al. NEJM 2021). Results: A total of 1954 pts with gBRCAm HER2− eBC were included (Table). Median age at diagnosis was 51 years among 1241 pts with HR+ eBC and 47 years among 713 pts with TNBC. Of 1010 pts with HR+ eBC who received adjuvant therapy, 217 (21%) received olaparib (including 19 pts who received olaparib before, 2 with, and 5 after CDK4/6i); 61 pts (6%) received CDK4/6i with endocrine therapy (ET) but without olaparib, 42 (4%) received IO without olaparib, and 282 (28%) received chemotherapy alone; 845 (84%) received ET, with or without other adjuvant therapies. Of 443 pts with TNBC who received adjuvant therapy, 162 (37%) received olaparib (93 received olaparib without IO; of 69 pts who received olaparib with IO, 18, notably, initiated olaparib before/concurrently with IO and 51 initiated olaparib after IO, including 50 within 27 weeks of initiating adjuvant IO); 196 (44%) pts received IO without olaparib and 82 (19%) received chemotherapy alone (including capecitabine in 8 pts). Among pts who received adjuvant therapy, 98/215 (46%) pts with high-risk HR+ eBC and 112/182 (62%) with high-risk TNBC received olaparib. Of 176 pts with TNBC without a pathological complete response (pCR) after neoadjuvant chemotherapy/IO, 90 (51%) did not receive olaparib. Among olaparib-treated pts, 119/217 (55%) with HR+ eBC and 50/162 (31%) with TNBC were not high risk. Conclusions: Real-world analysis showed that 40% of pts with gBRCAm, high-risk HER2− eBC did not receive adjuvant olaparib. Real-world olaparib use often did not align with restrictive criteria outlined in OlympiA, highlighting the need for comprehensive risk assessment to inform adjuvant treatment decisions in pts with gBRCAm HER2− eBC. Although prospective data is lacking, olaparib was frequently used concurrently with or after IO in pts with TNBC. Citation Format: S. Sardesai, M. Ru, X. Ma, C. Keane, J. Wang, M. Miranda, X. Xu, C. Isaacs. Real-world treatment patterns in 1954 US patients with HER2-negative early breast cancer and germline BRCA mutations (2021-2025) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-02-03.