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)

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.