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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
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
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 five 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 five years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
BRCA1, BRCA2, Breast cancer, Mutation, Risk-reducing salpingo-oophorectomy
1465-5411
Mavaddat, Nasim
bc5470a2-fb13-436d-ae0d-cc47bbedcc74
Antoniou, Antonis C.
65739e70-823d-4acd-b99a-12c7b5521f34
Mooij, Thea M.
f0067def-9188-4c28-92ae-2120b20cefe6
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
BCFR
Mavaddat, Nasim
bc5470a2-fb13-436d-ae0d-cc47bbedcc74
Antoniou, Antonis C.
65739e70-823d-4acd-b99a-12c7b5521f34
Mooij, Thea M.
f0067def-9188-4c28-92ae-2120b20cefe6
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23

Mavaddat, Nasim, Antoniou, Antonis C. and Mooij, Thea M. , BCFR (2020) Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Research, 22 (1), [8]. (doi:10.1186/s13058-020-1247-4).

Record type: 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 five 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 five years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

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Risk-reducing salpingo-oophorectomy - Version of Record
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More information

Accepted/In Press date: 5 January 2020
e-pub ahead of print date: 16 January 2020
Keywords: BRCA1, BRCA2, Breast cancer, Mutation, Risk-reducing salpingo-oophorectomy

Identifiers

Local EPrints ID: 437682
URI: http://eprints.soton.ac.uk/id/eprint/437682
ISSN: 1465-5411
PURE UUID: 0a43bcc9-96f8-44ee-86a7-ac45504c542d
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 11 Feb 2020 17:32
Last modified: 26 Nov 2021 02:34

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Contributors

Author: Nasim Mavaddat
Author: Antonis C. Antoniou
Author: Thea M. Mooij
Author: Diana Eccles ORCID iD
Corporate Author: BCFR

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