Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Simple Summary Approximately 15% of patients diagnosed with high-grade non-mucinous epithelial ovarian cancer (EOC) have a germline BRCA1/2 mutation, although all patients are often able to access germline testing. Importantly, the risk of familial ovarian cancer reduces with advancing age at diagnosis. The aim of our study was to determine the prevalence of germline and somatic BRCA1/2 mutations in women diagnosed with non-mucinous high-grade EOC aged ≥80. We found that somatic BRCA1/2 mutations occurred nine times more frequently than germline BRCA1/2 mutations in women aged ≥80. The only germline BRCA1/2 mutation reported in a patient aged ≥80 was detected in both germline and tumour DNA. These data suggest that germline BRCA1/2 testing in women diagnosed with high-grade non-mucinous EOC aged ≥80 can be reserved for those with a detectable tumour BRCA1/2 mutation. Abstract Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs.