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. 2020 Jan 16;22(1):8.
doi: 10.1186/s13058-020-1247-4.

Risk-reducing Salpingo-Oophorectomy, Natural Menopause, and Breast Cancer Risk: An International Prospective Cohort of BRCA1 and BRCA2 Mutation Carriers

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Free PMC article

Risk-reducing Salpingo-Oophorectomy, Natural Menopause, and Breast Cancer Risk: An International Prospective Cohort of BRCA1 and BRCA2 Mutation Carriers

Nasim Mavaddat et al. Breast Cancer Res. .
Free PMC article

Erratum in

  • Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
    Mavaddat N, Antoniou AC, Mooij TM, Hooning MJ, Heemskerk-Gerritsen BA; GENEPSO, Noguès C, Gauthier-Villars M, Caron O, Gesta P, Pujol P, Lortholary A; EMBRACE, Barrowdale D, Frost D, Evans DG, Izatt L, Adlard J, Eeles R, Brewer C, Tischkowitz M, Henderson A, Cook J, Eccles D; HEBON, van Engelen K, Mourits MJE, Ausems MGEM, Koppert LB, Hopper JL, John EM, Chung WK, Andrulis IL, Daly MB, Buys SS; kConFab Investigators, Benitez J, Caldes T, Jakubowska A, Simard J, Singer CF, Tan Y, Olah E, Navratilova M, Foretova L, Gerdes AM, Roos-Blom MJ, Van Leeuwen FE, Arver B, Olsson H, Schmutzler RK, Engel C, Kast K, Phillips KA, Terry MB, Milne RL, Goldgar DE, Rookus MA, Andrieu N, Easton DF; IBCCS, kConFab and BCFR. Mavaddat N, et al. Breast Cancer Res. 2020 Feb 26;22(1):25. doi: 10.1186/s13058-020-01259-w. Breast Cancer Res. 2020. PMID: 32102695 Free PMC article.

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: BRCA1; BRCA2; Breast cancer; Mutation; Risk-reducing salpingo-oophorectomy.

Conflict of interest statement

Wendy Chung reports potential conflict of interest from Regeneron and Biogen; Olivier Caron from AstraZeneca and IPSEN; Pascal Pujol, AstraZeneca, Genomic Health and Roche; D Gareth Evans, AstraZeneca and AmGen; Ros Eeles, Janssen-Cilag; Diane Eccles, Pierre Fabre, AstraZeneca; Karin Kast, Roche Pharma AG; and David Goldgar, University of Utah Foundation and Ambry Genetics. Anne-Marie Gerdes participated in an Advisory Board Meeting London in 2016, sponsored by Astra Zeneca about BRCA-testing in ovarian cancer.

Figures

Fig. 1
Fig. 1
Association between risk-reducing salpingo-oophorectomy and breast cancer risk for BRCA1 mutation carriers in each study centre category
Fig. 2
Fig. 2
Association between risk-reducing salpingo-oophorectomy and breast cancer risk for BRCA2 mutation carriers in each study centre category. HEBON and, for the 2–5-year category, kConFab were included in the “Other studies” category due to small numbers

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  • Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
    Mavaddat N, Antoniou AC, Mooij TM, Hooning MJ, Heemskerk-Gerritsen BA; GENEPSO, Noguès C, Gauthier-Villars M, Caron O, Gesta P, Pujol P, Lortholary A; EMBRACE, Barrowdale D, Frost D, Evans DG, Izatt L, Adlard J, Eeles R, Brewer C, Tischkowitz M, Henderson A, Cook J, Eccles D; HEBON, van Engelen K, Mourits MJE, Ausems MGEM, Koppert LB, Hopper JL, John EM, Chung WK, Andrulis IL, Daly MB, Buys SS; kConFab Investigators, Benitez J, Caldes T, Jakubowska A, Simard J, Singer CF, Tan Y, Olah E, Navratilova M, Foretova L, Gerdes AM, Roos-Blom MJ, Van Leeuwen FE, Arver B, Olsson H, Schmutzler RK, Engel C, Kast K, Phillips KA, Terry MB, Milne RL, Goldgar DE, Rookus MA, Andrieu N, Easton DF; IBCCS, kConFab and BCFR. Mavaddat N, et al. Breast Cancer Res. 2020 Feb 26;22(1):25. doi: 10.1186/s13058-020-01259-w. Breast Cancer Res. 2020. PMID: 32102695 Free PMC article.

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