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Published in: Breast Cancer Research 1/2020

Open Access 01-12-2020 | Salpingo-Oophorectomy | Research article

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

Authors: Nasim Mavaddat, Antonis C. Antoniou, Thea M. Mooij, Maartje J. Hooning, Bernadette A. Heemskerk-Gerritsen, Catherine Noguès, Marion Gauthier-Villars, Olivier Caron, Paul Gesta, Pascal Pujol, Alain Lortholary, Daniel Barrowdale, Debra Frost, D. Gareth Evans, Louise Izatt, Julian Adlard, Ros Eeles, Carole Brewer, Marc Tischkowitz, Alex Henderson, Jackie Cook, Diana Eccles, Klaartje van Engelen, Marian J. E. Mourits, Margreet G. E. M. Ausems, Linetta B. Koppert, John L. Hopper, Esther M. John, Wendy K. Chung, Irene L. Andrulis, Mary B. Daly, Saundra S. Buys, Javier Benitez, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Flora E. Van Leeuwen, Brita Arver, Håkan Olsson, Rita K. Schmutzler, Christoph Engel, Karin Kast, Kelly-Anne Phillips, Mary Beth Terry, Roger L. Milne, David E. Goldgar, Matti A. Rookus, Nadine Andrieu, Douglas F. Easton, GENEPSO, EMBRACE, HEBON, kConFab Investigators, on behalf of IBCCS, kConFab, BCFR

Published in: Breast Cancer Research | Issue 1/2020

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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.
Appendix
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Metadata
Title
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
Authors
Nasim Mavaddat
Antonis C. Antoniou
Thea M. Mooij
Maartje J. Hooning
Bernadette A. Heemskerk-Gerritsen
Catherine Noguès
Marion Gauthier-Villars
Olivier Caron
Paul Gesta
Pascal Pujol
Alain Lortholary
Daniel Barrowdale
Debra Frost
D. Gareth Evans
Louise Izatt
Julian Adlard
Ros Eeles
Carole Brewer
Marc Tischkowitz
Alex Henderson
Jackie Cook
Diana Eccles
Klaartje van Engelen
Marian J. E. Mourits
Margreet G. E. M. Ausems
Linetta B. Koppert
John L. Hopper
Esther M. John
Wendy K. Chung
Irene L. Andrulis
Mary B. Daly
Saundra S. Buys
Javier Benitez
Trinidad Caldes
Anna Jakubowska
Jacques Simard
Christian F. Singer
Yen Tan
Edith Olah
Marie Navratilova
Lenka Foretova
Anne-Marie Gerdes
Marie-José Roos-Blom
Flora E. Van Leeuwen
Brita Arver
Håkan Olsson
Rita K. Schmutzler
Christoph Engel
Karin Kast
Kelly-Anne Phillips
Mary Beth Terry
Roger L. Milne
David E. Goldgar
Matti A. Rookus
Nadine Andrieu
Douglas F. Easton
GENEPSO
EMBRACE
HEBON
kConFab Investigators
on behalf of IBCCS
kConFab
BCFR
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-1247-4

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