Abstract PS2-06-30: Real-world uptake of gBRCA testing as a companion diagnostic for olaparib in patients with HER2-negative recurrent high-risk early breast cancer in Japan: a cross-sectional multicenter study (BRCAwareness)

Abstract Background In patients (pts) with HER2-negative, high-risk early breast cancer (BC), adjuvant (adj) olaparib (OLA) significantly improves invasive disease-free survival and overall survival in those carrying germline BRCA1 or BRCA2 (gBRCA) pathogenic variants (PVs) 1). To optimize clinical outcomes, timely gBRCA testing as a companion diagnostic is essential. However, the real-world uptake of gBRCA testing in this population remains unclear. Methods We enrolled newly diagnosed pts with invasive HER2-negative BC who underwent curative surgery from January 1, 2023 to December 31, 2023 in Japan. Patient selection was based on the inclusion criteria from the OlympiA trial1). Specifically, ER-positive pts required either ≥ 4 positive lymph nodes after surgery or non-pathological complete response (pCR) with a CPS+EG score ≥ 3 following neoadjuvant chemotherapy (NAC). ER-negative pts required an invasive tumor 2 cm or ≥ 1 nodal metastasis after surgery, or non-pCR after NAC. Furthermore, we collected both patient-level and institutional data. The primary outcome was the proportion of pts who underwent gBRCA testing. Secondary outcomes included: (1) factors linked to no testing; (2) proportion of PVs among those tested; (3) proportion of pts with gBRCA PVs who started OLA; and (4) other treatments used in pts with gBRCA PVs not receiving OLA. Based on a previous U.S. report in which 87% of young women with BC underwent gBRCA testing2), we hypothesized that at least 88% of eligible pts should be tested. Assuming an expected testing rate of 88%, a sample size of 688 pts was required to maintain a 95% confidence interval (CI) width of 0.05. The target sample size was set at 700 to account for potential exclusions. Results Of 824 pts recruited from 46 facilities during the primary enrollment, 700 were randomly selected for secondary registration. After excluding 9 ineligible pts, a total of 691 were analyzed. The median age was 62 20-96 years, 99% were female, 52 had bilateral BC, 157 had a family history of BC, and 18 had dementia. ER status was positive in 51%. NAC was administered to 362 pts (52%), including 148 (21%) with ER-positive BC, while 199 (29%) ER-positive BC pts had upfront surgery. Regarding facility characteristics, the median number of breast cancer specialists per facility was 3 1-17, and genetic counselors were available in 27 facilities (59%). gBRCA testing was performed in 437 of 691 pts (63.2%; 95% CI, 59.5-66.9). Of 254 untested patients, 168 (66%) were not informed, mainly due to physician oversight (57%) or perceived ineligibility related to age, comorbidities, or treatment refusal (40%). Among 69 pts who were informed but declined testing, the reasons for no testing were psychological distress (46%), cost of testing (35%), and concerns about genetic implications for family members (12%). Among 42 pts (9.6%) with gBRCA PVs (10 pts were ER-positive), 32 received OLA. Of the remaining 10, all but 3 had perioperative chemotherapy, and none received abemaciclib. Results of our multivariate analysis on missed testing will be presented at the conference. Conclusions Despite its clinical importance as a companion diagnostic for adj OLA, timely gBRCA testing was underutilized in the real world. Two-thirds of untested pts were not informed of the testing option, highlighting a potential gap between clinical trial evidence and practice. To ensure equitable access to adj OLA, greater efforts are needed to improve physician awareness and streamline institutional workflows supporting genetic testing. References 1) Geyer CE et al. Ann Oncol. 2022;33(12):1250-1268. 2) Rosenberg SM et al. JAMA Oncol. 2016;2(6):730-736. Citation Format: T. Taji, Y. Uemura, Y. Kimura, N. Maeda, A. Ito, H. Seki, D. Takabatake, M. Harao, S. Nakamoto, R. Matsunuma, C. Koganezawa, T. Iwamoto, H. Mukai, Y. Kikawa. Real-world uptake of gBRCA testing as a companion diagnostic for olaparib in patients with HER2-negative recurrent high-risk early breast cancer in Japan: a cross-sectional multicenter study (BRCAwareness) 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 PS2-06-30.