Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
Posted on 2020-01-29 - 04:39
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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Mavaddat, Nasim; Antoniou, Antonis; Mooij, Thea; Hooning, Maartje; Heemskerk-Gerritsen, Bernadette; Noguès, Catherine; et al. (2020). Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4821051.v2
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AUTHORS (56)
NM
Nasim Mavaddat
AA
Antonis Antoniou
TM
Thea Mooij
MH
Maartje Hooning
BH
Bernadette Heemskerk-Gerritsen
CN
Catherine Noguès
MG
Marion Gauthier-Villars
OC
Olivier Caron
PG
Paul Gesta
PP
Pascal Pujol
AL
Alain Lortholary
DB
Daniel Barrowdale
DF
Debra Frost
DE
D. Evans
LI
Louise Izatt
JA
Julian Adlard
RE
Ros Eeles
CB
Carole Brewer
MT
Marc Tischkowitz
AH
Alex Henderson