TY - JOUR
T1 - European experts consensus
T2 - BRCA/homologous recombination deficiency testing in first-line ovarian cancer
AU - European experts’ consensus group
AU - Vergote, I.
AU - González-Martín, A.
AU - Ray-Coquard, I.
AU - Harter, P.
AU - Colombo, N.
AU - Pujol, P.
AU - Lorusso, D.
AU - Mirza, M. R.
AU - Brasiuniene, B.
AU - Madry, R.
AU - Brenton, J. D.
AU - Ausems, M. G.E.M.
AU - Büttner, R.
AU - Lambrechts, D.
AU - Ausems, M.
AU - Brenton, J.
AU - Abreu, M.
AU - Balboni, S.
AU - Banerjee, S.
AU - Barberis, M.
AU - Barretina Ginesta, M. P.
AU - Baurain, J. F.
AU - Bignami, M.
AU - Bjorge, L.
AU - Blecharz, P.
AU - Bruchim, I.
AU - Capilna, M.
AU - Cerana, N.
AU - Cicchetti, A.
AU - Collins, D.
AU - Concin, N.
AU - D'Incalci, M.
AU - Davidson, B.
AU - de la Motte Rouge, T.
AU - De Iaco, P.
AU - Demirkiran, F.
AU - Denys, H.
AU - Doerk, T.
AU - Dorum, A.
AU - Ferrero, A.
AU - Fidalgo, A. P.
AU - Genuardi, M.
AU - Gladieff, L.
AU - Glasspool, R.
AU - Grimm, C.
AU - Gultekin, M.
AU - Hahnen, E.
AU - Hasenburg, A.
AU - Hegmane, A.
AU - Pikarsky, E.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. 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 Preferred Reporting Items for Systematic Reviews and Meta-analyses 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.
AB - Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. 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 Preferred Reporting Items for Systematic Reviews and Meta-analyses 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.
KW - BRCA1/2
KW - PARP inhibition
KW - genetic counselling
KW - homologous recombination deficiency
KW - mainstream genetic testing
KW - ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85123182521&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2021.11.013
DO - 10.1016/j.annonc.2021.11.013
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C2 - 34861371
AN - SCOPUS:85123182521
SN - 0923-7534
VL - 33
SP - 276
EP - 287
JO - Annals of Oncology
JF - Annals of Oncology
IS - 3
ER -
