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

N. Mavaddat*, A.C. Antoniou, T.M. Mooij, M.J. Hooning, B.A. Heemskerk-Gerritsen, C. Nogues, L. Laborde, E. Breysse, D. Stoppa-Lyonnet, M. Gauthier-Villars, B. Buecher, O. Caron, E. Fourme-Mouret, J.P. Fricker, C. Lasset, V. Bonadona, P. Berthet, L. Faivre, E. Luporsi, V. MariL. Gladieff, P. Gesta, H. Sobol, F. Eisinger, M. Longy, C. Dugast, C. Colas, I. Coupier, P. Pujol, C. Corsini, A. Lortholary, P. Vennin, C. Adenis, T.D. Nguyen, C. Delnatte, J. Tinat, I. Tennevet, J.M. Limacher, C. Maugard, Y.J. Bignon, L. Demange, C. Penet, H. Dreyfus, O. Cohen-Haguenauer, L. Venat-Bouvet, D. Leroux, H. Zattara-Cannoni, S. Fert-Ferrer, Breast Cancer Family Registry (BCFR), EMBRACE, GENEPSO, HEBON, Marinus Blok, IBCCS, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), KConFab Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number8
Number of pages11
JournalBreast Cancer Research
Issue number1
Publication statusPublished - 16 Jan 2020


  • BRCA1
  • BRCA2
  • Breast cancer
  • LINK
  • Mutation
  • Risk-reducing salpingo-oophorectomy
  • association
  • brca1
  • brca2
  • breast cancer
  • consortium
  • kconfab
  • link
  • metaanalysis
  • mutation
  • ovarian
  • reduction
  • risk-reducing salpingo-oophorectomy
  • surgery
  • survival
  • women

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