Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
Authors
Antoniou, Antonis C.
Mooij, Thea M.
Hooning, Maartje J.
Heemskerk-Gerritsen, Bernadette A.
Noguès, Catherine
Gauthier-Villars, Marion
Caron, Olivier
Gesta, Paul
Pujol, Pascal
Lortholary, Alain
Barrowdale, Daniel
Frost, Debra
Evans, D. Gareth
Izatt, Louise
Adlard, Julian
Eeles, Ros
Brewer, Carole
Tischkowitz, Marc
Henderson, Alex
Cook, Jackie
Eccles, Diana
van Engelen, Klaartje
Mourits, Marian J. E.
Ausems, Margreet G. E. M.
Koppert, Linetta B.
Hopper, John L.
John, Esther M.
Chung, Wendy K.
Andrulis, Irene L.
Daly, Mary B.
Buys, Saundra S.
Benitez, Javier
Caldes, Trinidad
Jakubowska, Anna
Simard, Jacques
Singer, Christian F.
Tan, Yen
Olah, Edith
Navratilova, Marie
Foretova, Lenka
Gerdes, Anne-Marie
Roos-Blom, Marie-José
Van Leeuwen, Flora E.
Arver, Brita
Olsson, Håkan
Schmutzler, Rita K.
Engel, Christoph
Kast, Karin
Phillips, Kelly-Anne
Terry, Mary Beth
Milne, Roger L.
Goldgar, David E.
Rookus, Matti A.
Andrieu, Nadine
Easton, Douglas F.
Laborde, Lilian
Breysse, Emmanuel
Stoppa-Lyonnet, Dominique
Buecher, Bruno
Fourme-Mouret, Emmanuelle
Fricker, Jean-Pierre
Lasset, Christine
Bonadona, Valérie
Berthet, Pascaline
Faivre, Laurence
Luporsi, Elisabeth
Mari, Véronique
Gladieff, Laurence
Sobol, Hagay
Eisinger, François
Longy, Michel
Dugast, Catherine
Colas, Chrystelle
Coupier, Isabelle
Corsini, Carole
Vennin, Philippe
Adenis, Claude
Nguyen, Tan Dat
Delnatte, Capucine
Tinat, Julie
Tennevet, Isabelle
Limacher, Jean-Marc
Maugard, Christine
Bignon, Yves-Jean
Demange, Liliane
Penet, Clotilde
Dreyfus, Hélène
Cohen-Haguenauer, Odile
Venat-Bouvet, Laurence
Leroux, Dominique
Zattara-Cannoni, Hélène
Fert-Ferrer, Sandra
Bera, Odile
Ellis, Steve
Hogervorst, F. B. L.
Collée, J. M.
van Asperen, C. J.
Mensenkamp, A. R.
Ausems, M. G. E. M.
Meijers-Heijboer, H. E. J.
van Engelen, K.
Blok, M. J.
Oosterwijk, J. C.
Verloop, J.
van den Broek, E.
Publication Date
2020-01-16Journal Title
Breast Cancer Research
Publisher
BioMed Central
Volume
22
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Mavaddat, N., Antoniou, A. C., Mooij, T. M., Hooning, M. J., Heemskerk-Gerritsen, B. A., Noguès, C., Gauthier-Villars, M., et al. (2020). Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Research, 22 (1) https://doi.org/10.1186/s13058-020-1247-4
Abstract
Abstract: Background: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. Methods: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. Results: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94–1.61) or BRCA2 (HR = 0.88; 95% CI 0.62–1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. Conclusion: We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
Keywords
Research Article, Breast cancer, BRCA1, BRCA2, Mutation, Risk-reducing salpingo-oophorectomy
Sponsorship
Cancer Research UK (C1287/A17523, C1287/23382, C1287/A16563, C12292/A20861, C12292/A11174)
National Cancer Institute (UM1 CA164920)
German Cancer Aid (grant no 110837)
European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, n°2014-008)
Dutch Cancer Society (NKI1998-1854, NKI2007-3756)
Dutch Cancer Society (NKI2004-3088)
Genome Canada and the Canadian Institutes of Health Research (GPH-129344)
Identifiers
s13058-020-1247-4, 1247
External DOI: https://doi.org/10.1186/s13058-020-1247-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316237
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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