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

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@article{1ce59a62b8ce408cbadb821f9b0f10b7,
title = "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.",
keywords = "BRCA1, BRCA2, Breast cancer, Mutation, Risk-reducing salpingo-oophorectomy",
author = "Nasim Mavaddat and Antoniou, {Antonis C} and Mooij, {Thea M} and Hooning, {Maartje J} and Heemskerk-Gerritsen, {Bernadette A} and Catherine Nogu{\`e}s and Marion Gauthier-Villars and Olivier Caron and Paul Gesta and Pascal Pujol and Alain Lortholary and Daniel Barrowdale and Debra Frost and Evans, {D Gareth} and Louise Izatt and Julian Adlard and Ros Eeles and Carole Brewer and Marc Tischkowitz and Alex Henderson and Jackie Cook and Diana Eccles and {van Engelen}, Klaartje and Mourits, {Marian J E} and Ausems, {Margreet G E M} and Koppert, {Linetta B} and Hopper, {John L} and John, {Esther M} and Chung, {Wendy K} and Andrulis, {Irene L} and Daly, {Mary B} and Buys, {Saundra S} and Javier Benitez and Trinidad Caldes and Anna Jakubowska and Jacques Simard and Singer, {Christian F} and Yen Tan and Edith Olah and Marie Navratilova and Lenka Foretova and Anne-Marie Gerdes and Marie-Jos{\'e} Roos-Blom and {Van Leeuwen}, {Flora E} and Brita Arver and H{\aa}kan Olsson and Schmutzler, {Rita K} and Christoph Engel and Karin Kast and Kelly-Anne Phillips and GENEPSO",
year = "2020",
month = jan,
day = "16",
doi = "10.1186/s13058-020-1247-4",
language = "English",
volume = "22",
pages = "8",
journal = "Breast Cancer Research",
issn = "1465-542X",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk

T2 - an international prospective cohort of BRCA1 and BRCA2 mutation carriers

AU - Mavaddat, Nasim

AU - Antoniou, Antonis C

AU - Mooij, Thea M

AU - Hooning, Maartje J

AU - Heemskerk-Gerritsen, Bernadette A

AU - Noguès, Catherine

AU - Gauthier-Villars, Marion

AU - Caron, Olivier

AU - Gesta, Paul

AU - Pujol, Pascal

AU - Lortholary, Alain

AU - Barrowdale, Daniel

AU - Frost, Debra

AU - Evans, D Gareth

AU - Izatt, Louise

AU - Adlard, Julian

AU - Eeles, Ros

AU - Brewer, Carole

AU - Tischkowitz, Marc

AU - Henderson, Alex

AU - Cook, Jackie

AU - Eccles, Diana

AU - van Engelen, Klaartje

AU - Mourits, Marian J E

AU - Ausems, Margreet G E M

AU - Koppert, Linetta B

AU - Hopper, John L

AU - John, Esther M

AU - Chung, Wendy K

AU - Andrulis, Irene L

AU - Daly, Mary B

AU - Buys, Saundra S

AU - Benitez, Javier

AU - Caldes, Trinidad

AU - Jakubowska, Anna

AU - Simard, Jacques

AU - Singer, Christian F

AU - Tan, Yen

AU - Olah, Edith

AU - Navratilova, Marie

AU - Foretova, Lenka

AU - Gerdes, Anne-Marie

AU - Roos-Blom, Marie-José

AU - Van Leeuwen, Flora E

AU - Arver, Brita

AU - Olsson, Håkan

AU - Schmutzler, Rita K

AU - Engel, Christoph

AU - Kast, Karin

AU - Phillips, Kelly-Anne

AU - GENEPSO

PY - 2020/1/16

Y1 - 2020/1/16

N2 - 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.

AB - 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.

KW - BRCA1

KW - BRCA2

KW - Breast cancer

KW - Mutation

KW - Risk-reducing salpingo-oophorectomy

UR - http://www.scopus.com/inward/record.url?scp=85078031432&partnerID=8YFLogxK

U2 - 10.1186/s13058-020-1247-4

DO - 10.1186/s13058-020-1247-4

M3 - Journal article

C2 - 31948486

VL - 22

SP - 8

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-542X

IS - 1

M1 - 8

ER -

ID: 59748672