BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for both germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive NMEOC cases (n=388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.7%) were detected in 350 cases with germline BRCA1/2 (gBRCA) wild-type. All sBRCA PVs were detected in non-familial cases. By analysing our full germline BRCA1/2 database, there were gBRCA PV detected in 92/1114 (8.3%) non-familial (only 3% ≥70 years old) and 245/641 (38.2%) in familial NMEOC cases. Germline non-familial cases were dominated by BRCA2 in older women (8/271 ≥70 years old, all BRCA2; P=0.005). The ratio of sBRCA-to-gBRCA was ≤1.0 in women aged <70 years old, compared to 5.2 in women aged ≥70 years old (P=0.005). The likelihood of missed germline BRCA1/2 PVs (copy-number variants missed on most somatic assays) by only testing tumour DNA was 0.4% in women aged ≥70 years old. We recommend reflex tumour BRCA1/2 testing in all NMEOC cases, and that gBRCA testing is not required for women aged ≥70 years old with no identifiable tumour BRCA1/2 PV and/or no family history of breast, ovarian, prostate and/or pancreatic cancer.