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

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

1 déc. 2020Breast Cancer Research

Auteurs

Nasim Mavaddat, , Antonis C. Antoniou, Thea M. Mooij, Maartje J. Hooning, Bernadette A. Heemskerk-Gerritsen, Catherine Noguès, Marion Gauthier-Villars, Olivier Caron, Paul Gesta, Pascal Pujol, Alain Lortholary, Daniel Barrowdale, Debra Frost, D. Gareth Evans, Louise Izatt, Julian Adlard, Ros Eeles, Carole Brewer, Marc Tischkowitz, Alex Henderson, Jackie Cook, Diana Eccles, Klaartje van Engelen, Marian J. E. Mourits, Margreet G. E. M. Ausems, Linetta B. Koppert, John L. Hopper, Esther M. John, Wendy K. Chung, Irene L. Andrulis, Mary B. Daly, Saundra S. Buys, Javier Benitez, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Flora E. Van Leeuwen, Brita Arver, Håkan Olsson, Rita K. Schmutzler, Christoph Engel, Karin Kast, Kelly-Anne Phillips, Mary Beth Terry, Roger L. Milne, David E. Goldgar, Matti A. Rookus, Nadine Andrieu, Douglas F. Easton, , , , , ,

Résumé

Abstract

Background

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.

Methods

A multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation 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 forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation 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 forBRCA2mutation 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 forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation 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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