Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers - Archive ouverte HAL Access content directly
Journal Articles Breast Cancer Research Year : 2020

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

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Maartje Hooning
  • Function : Author
  • PersonId : 910045
Alain Lortholary
  • Function : Author
  • PersonId : 928991
Daniel Barrowdale
  • Function : Author
  • PersonId : 920604
Debra Frost
  • Function : Author
  • PersonId : 909872
Louise Izatt
  • Function : Author
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Julian Adlard
  • Function : Author
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Ros Eeles
  • Function : Author
  • PersonId : 909874
Carole Brewer
  • Function : Author
  • PersonId : 909882
Jackie Cook
  • Function : Author
  • PersonId : 909879
Margreet Ausems
  • Function : Author
  • PersonId : 909901
Esther John
  • Function : Author
  • PersonId : 922703
Wendy Chung
  • Function : Author
  • PersonId : 920701
Mary Daly
  • Function : Author
  • PersonId : 909906
Saundra Buys
  • Function : Author
  • PersonId : 909902
Anna Jakubowska
  • Function : Author
  • PersonId : 906670
Jacques Simard
  • Function : Author
  • PersonId : 920660
Christian Singer
  • Function : Author
  • PersonId : 910055
Brita Arver
  • Function : Author
Karin Kast
  • Function : Author
  • PersonId : 922731

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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Dates and versions

inserm-02445596 , version 1 (20-01-2020)

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Nasim Mavaddat, Antonis C. Antoniou, Thea Mooij, Maartje Hooning, Bernadette Heemskerk-Gerritsen, et al.. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Research, 2020, 22 (1), pp.8. ⟨10.1186/s13058-020-1247-4⟩. ⟨inserm-02445596⟩
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