Title European Experts Consensus: BRCA/Homologous Recombination Deficiency Testing in First-Line Ovarian Cancer /
Authors Vergote, I ; González-Martín, A ; Ray-Coquard, I ; Harter, P ; Colombo, N ; Pujol, P ; Lorusso, D ; Mirza, M.R ; Brasiūnienė, Birutė ; Madry, R ; Brenton, J.D ; Ausems, M.G.E.M ; Büttner, R ; Lambrechts, D
DOI 10.1016/j.annonc.2021.11.013
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Is Part of Annals of oncology.. Amsterdam : Elsevier. 2022, vol. 33, iss. 3, p. 276-287.. ISSN 0923-7534. eISSN 1569-8041
Keywords [eng] Ovarian cancer ; BRCA1/2, homologous recombination deficiency ; PARP inhibition ; genetic counselling ; mainstream genetic testing
Abstract [eng] Background Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. Homologous recombination repair deficiency (HRR deficiency) is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (N=14) and contributors (N=84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the PRISMA guidelines. Results A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
Published Amsterdam : Elsevier
Type Journal article
Language English
Publication date 2022
CC license CC license description