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Review
. 2022 Jul;127(1):163-167.
doi: 10.1038/s41416-022-01773-y. Epub 2022 Mar 8.

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

Robert D Morgan  1   2 , George J Burghel  3 , Nicola Flaum  4   5 , Michael Bulman  3 , Philip Smith  3 , Andrew R Clamp  4   6 , Jurjees Hasan  4 , Claire L Mitchell  4 , Zena Salih  4 , Emma R Woodward  5   7 , Fiona Lalloo  7 , Emma J Crosbie  6   8 , Richard J Edmondson  6   8 , Andrew J Wallace  3 , Gordon C Jayson  4   6 , D Gareth R Evans  5   7
Affiliations
Review

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

Robert D Morgan et al. Br J Cancer. 2022 Jul.

Abstract

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (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 regional germline BRCA1/2 database there were 92/1114 (8.3%) gBRCA PVs detected in non-familial cases (only 3% ≥70 years old) and 245/641 (38.2%) in familial cases. Germline non-familial cases were dominated by BRCA2 in older women (8/271 ≥ 70 years old, all BRCA2). 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 testing only 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 family history of breast, ovarian, prostate and/or pancreatic cancer.

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Conflict of interest statement

RDM, GJB, NF, MB, PS, JH, CLM, ZS, ERW, FL, EJC, RJE, AJW and DGRE declare no competing interests. GCJ declares research funding from AstraZeneca for investigator-led clinical trials. ARC declares research funding and advisory boards fees from AstraZeneca, and speaker and advisory board fees from Clovis Oncology.

Figures

Fig. 1
Fig. 1. Flow chart for germline and tumour BRCA1/2 testing.
Paired germline and tumour testing was requested in 409 patients. In total, 1755 patients underwent germline testing.
See this image and copyright information in PMC

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