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 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.
BRCA1, BRCA2, Breast cancer, Mutation, Risk-reducing salpingo-oophorectomy
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
16 January 2020
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).
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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Risk-reducing salpingo-oophorectomy
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Accepted/In Press date: 5 January 2020
e-pub ahead of print date: 16 January 2020
Published date: 16 January 2020
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Publisher Copyright:
© 2020 The Author(s).
Keywords:
BRCA1, BRCA2, Breast cancer, Mutation, Risk-reducing salpingo-oophorectomy
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Local EPrints ID: 437682
URI: http://eprints.soton.ac.uk/id/eprint/437682
ISSN: 1465-5411
PURE UUID: 0a43bcc9-96f8-44ee-86a7-ac45504c542d
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Date deposited: 11 Feb 2020 17:32
Last modified: 17 Mar 2024 02:36
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Author:
Nasim Mavaddat
Author:
Antonis C. Antoniou
Author:
Thea M. Mooij
Corporate Author: BCFR
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