BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?
Morgan, Robert David Burghel, GJ Flaum, Nicola Bulman, M Smith, P Clamp, Andrew R Hasan, Jurjees Mitchell, Claire L Salih, Zena Woodward, E R
Morgan, Robert David
Burghel, GJ
Flaum, Nicola
Bulman, M
Smith, P
Clamp, Andrew R
Hasan, Jurjees
Mitchell, Claire L
Salih, Zena
Woodward, E R
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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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Date
2022
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Morgan, R D, Burghel, G J, Flaum, N, Bulman, M, Smith, P, Clamp, A R, Hasan, J, Mitchell, C L, Salih, Z, Woodward, E R, Lalloo, F, Crosbie, E J, Edmondson, R J, Wallace, A J, Jayson, G C, Evans, D G R. BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing? British Journal of Cancer. 2022 Mar 8