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


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.

SUBMITTER: Mavaddat N 

PROVIDER: S-EPMC6966793 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Mavaddat Nasim N   Antoniou Antonis C AC   Mooij Thea M TM   Hooning Maartje J MJ   Heemskerk-Gerritsen Bernadette A BA   Noguès Catherine C   Gauthier-Villars Marion M   Caron Olivier O   Gesta Paul P   Pujol Pascal P   Lortholary Alain A   Barrowdale Daniel D   Frost Debra D   Evans D Gareth DG   Izatt Louise L   Adlard Julian J   Eeles Ros R   Brewer Carole C   Tischkowitz Marc M   Henderson Alex A   Cook Jackie J   Eccles Diana D   van Engelen Klaartje K   Mourits Marian J E MJE   Ausems Margreet G E M MGEM   Koppert Linetta B LB   Hopper John L JL   John Esther M EM   Chung Wendy K WK   Andrulis Irene L IL   Daly Mary B MB   Buys Saundra S SS   Benitez Javier J   Caldes Trinidad T   Jakubowska Anna A   Simard Jacques J   Singer Christian F CF   Tan Yen Y   Olah Edith E   Navratilova Marie M   Foretova Lenka L   Gerdes Anne-Marie AM   Roos-Blom Marie-José MJ   Van Leeuwen Flora E FE   Arver Brita B   Olsson Håkan H   Schmutzler Rita K RK   Engel Christoph C   Kast Karin K   Phillips Kelly-Anne KA   Terry Mary Beth MB   Milne Roger L RL   Goldgar David E DE   Rookus Matti A MA   Andrieu Nadine N   Easton Douglas F DF  

Breast cancer research : BCR 20200116 1


<h4>Background</h4>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.<h4>Methods</h4>A multi-centre prospective cohort of 2272 BRCA1 and 1605  ...[more]

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