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

Abstract Background Adjuvant olaparib significantly improves invasive disease-free and overall survival in high-risk human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer patients carrying germline breast cancer susceptibility gene 1/2 ( gBRCA ) pathogenic variants (PVs). Timely gBRCA testing as a companion diagnostic for adjuvant olaparib is essential. However, its real-world uptake remains unclear. Methods We enrolled patients with invasive HER2-negative early breast cancer who underwent curative surgery during 2023 in Japan. Eligibility was based on the OlympiA trial criteria. Estrogen receptor (ER)-positive patients required ≥ 4 positive nodes after surgery or non-pathological complete response (non-pCR) with clinical and pathologic stage (CPS) and estrogen receptor status and histologic grade (EG) score ≥ 3 following neoadjuvant chemotherapy (NAC). ER-negative patients required invasive tumor > 2 cm or ≥ 1 nodal metastasis after surgery, or non-pCR after NAC. The primary outcome was gBRCA testing rate; secondary outcomes included a proportion of patients with gBRCA PVs and a proportion of patients starting adjuvant olaparib. We also explored factors associated with not undergoing testing. Results Of 824 patients enrolled from 46 facilities, 691 were analyzed after random sampling and exclusions. The testing rate was 63.2% (95% confidence interval 59.5–66.9). Among 254 untested patients, 168 (66%) were not informed—mainly due to physician oversight in recognizing eligibility (57%) or physician-perceived patient ineligibility (40%). Of 69 informed but untested patients, reasons included psychological distress (46%), testing cost (35%), and familial concerns (12%). Of 42 patients (9.6%) with gBRCA PVs, 32 received olaparib. Multivariable analysis (female only) showed that age ≥ 65 years, postmenopausal status, major comorbidities, upfront surgery, absence of family history of hereditary breast and ovarian cancer-related cancers, and absence of bilateral or multiple primary breast cancers were associated with lower testing rates. Conclusion Greater physician awareness of companion diagnostic is needed to ensure timely gBRCA testing and equitable access to adjuvant olaparib.