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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 Paul Gesta 7 Pascal Pujol 8 Alain Lortholary 9 Daniel Barrowdale 1 Debra Frost 1 D. Gareth Evans 10 Louise Izatt 11 Julian Adlard 12, 13 Ros Eeles 14 Carole Brewer 15 Marc Tischkowitz 1 Alex Henderson 16 Jackie Cook 17 Diana Eccles 18 Klaartje van Engelen 19 Marian Mourits 20 Margreet Ausems 21 Linetta Koppert 3 John Hopper 22 Esther John 23 Wendy Chung 24 Irene Andrulis 25 Mary Daly 26 Saundra Buys 27 Javier Benitez 28 Trinidad Caldés 29 Anna Jakubowska 30 Jacques Simard 31 Christian Singer 32 Yen Tan 33 Edith Olah 34 Marie Navratilova 35 Lenka Foretova 36 Anne-Marie Gerdes 37 Marie-José Roos-Blom 38 Flora van Leeuwen 38 Brita Arver 39 Håkan Olsson 40 Rita Schmutzler 41 Christoph Engel 42 Karin Kast 43 Kelly-Anne Phillips 44 Mary Beth Terry 45 Roger Milne 46 David Goldgar 47 Matti Rookus 48 Nadine Andrieu 49, 50 Douglas Easton 51
45 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⟩

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