Is reflex germline BRCA1/2 testing necessary in women diagnosed with non-mucinous high-grade epithelial ovarian cancer aged 80 years or older?

Robert D. Morgan, George J. Burghel, Nicola Flaum, Michael Bulman, Philip Smith, Andrew R. Clamp, Jurjees Hasan, Claire Mitchell, Zena Salih, Emma R. Woodward, Fiona I. Lalloo , Emma J. Crosbie, Richard J. Edmondson, Helene Schlecht, Gordon C. Jayson, D. Gareth R. Evans

Research output: Contribution to journalArticlepeer-review

Abstract

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflexed tested for germline and tumor 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 tumor 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 tumor testing for Homologous Recombination deficiency (HRD) using Myriad’s myChoice CDx. Seven-hundred-and-two patients successfully underwent both germline and tumor BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 likely pathogenic/pathogenic variants (LP/PVs) were detected nine times more often than germline BRCA1/2 LP/PVs (ratio 9:1). The only germline PV reported in a patient aged ≥80 was detected in germline and tumor DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline LP/PV in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggests that tumor 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 tumor BRCA1/2 LP/PV.
Original languageEnglish
JournalCancers
Volume15
Issue number3
DOIs
Publication statusPublished - 25 Jan 2023

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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