Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
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Date
2020-01-16ICR Author
Author
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, A-M
Roos-Blom, M-J
Van Leeuwen, FE
Arver, B
Olsson, H
Schmutzler, RK
Engel, C
Kast, K
Phillips, K-A
Terry, MB
Milne, RL
Goldgar, DE
Rookus, MA
Andrieu, N
Easton, DF
IBCCS,
kConFab,
BCFR,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
GENEPSO
EMBRACE
HEBON
kConFab Investigators
IBCCS
kConFab
BCFR
Humans
Breast Neoplasms
BRCA1 Protein
BRCA2 Protein
Incidence
Cohort Studies
Prospective Studies
Risk Reduction Behavior
Menopause
Mutation
Adult
Middle Aged
International Agencies
Female
Salpingo-oophorectomy
Research team
Oncogenetics
Language
eng
Date accepted
2020-01-05
License start date
2020-01-16
Citation
Breast cancer research : BCR, 2020, 22 (1), pp. 8 - ?
Publisher
BMC