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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers

Nasim Mavaddat 1 Antonis Antoniou 1 Thea Mooij 2 Maartje Hooning 3 Bernadette Heemskerk-Gerritsen 3 Catherine Noguès 4 Marion Gauthier-Villars 5 Olivier Caron 6, 7 Paul Gesta 8 Pascal Pujol 9 Alain Lortholary 10 Daniel Barrowdale 1 Debra Frost 1 D. Gareth Evans 11 Louise Izatt 12 Julian Adlard 13, 14 Ros Eeles 15 Carole Brewer 16 Marc Tischkowitz 1 Alex Henderson 17 Jackie Cook 18 Diana Eccles 19 Klaartje van Engelen 20 Marian Mourits 21 Margreet Ausems 22 Linetta Koppert 3 John Hopper 23 Esther John 24 Wendy Chung 25 Irene Andrulis 26 Mary Daly 27 Saundra Buys 28 Javier Benitez 29 Trinidad Caldés 30 Anna Jakubowska 31 Jacques Simard 32 Christian Singer 33 Yen Tan 34 Edith Olah 35 Marie Navratilova 36 Lenka Foretova 37 Anne-Marie Gerdes 38 Marie-José Roos-Blom 39 Flora van Leeuwen 39 Brita Arver 40 Håkan Olsson 41 Rita Schmutzler 42 Christoph Engel 43 Karin Kast 44 Kelly-Anne Phillips 45 Mary Beth Terry 46 Roger Milne 47 David Goldgar 48 Matti Rookus 49 Nadine Andrieu 50, 51 Douglas Easton 52
46 Department of Epidemiology [Columbia University]
Columbia Mailman School of Public Health, Columbia University [New York]
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.
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Nasim Mavaddat, Antonis Antoniou, Thea Mooij, Maartje Hooning, Bernadette Heemskerk-Gerritsen, et al.. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Research, BioMed Central, 2020, 22 (1), pp.8. ⟨10.1186/s13058-020-1247-4⟩. ⟨inserm-02445596⟩