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

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; on behalf of IBCCS, kConFab and BCFR

doi:10.1186/s13058-020-1247-4

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

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 HendersonJackie 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, on behalf of IBCCS, kConFab and BCFR

Medicine Monash Health

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47 Citations (Scopus)

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.

Original language	English
Article number	8
Number of pages	11
Journal	Breast Cancer Research
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s13058-020-1247-4
Publication status	Published - 16 Jan 2020

Keywords

BRCA1
BRCA2
Breast cancer
Mutation
Risk-reducing salpingo-oophorectomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13058-020-1247-4Licence: CC BY

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Mavaddat, N., Antoniou, A. C., Mooij, T. M., Hooning, M. J., Heemskerk-Gerritsen, B. A., Noguès, C., Gauthier-Villars, M., Caron, O., Gesta, P., Pujol, P., Lortholary, A., Barrowdale, D., Frost, D., Evans, D. G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., ... on behalf of IBCCS, kConFab and BCFR (2020). Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Research, 22(1), Article 8. https://doi.org/10.1186/s13058-020-1247-4

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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 Gerdes, {Anne Marie} and Roos-Blom, {Marie Jos{\'e}} and {Van Leeuwen}, {Flora E.} and Brita Arver and H{\aa}kan Olsson and Schmutzler, {Rita K.} and Christoph Engel and Karin Kast and Phillips, {Kelly Anne} and Terry, {Mary Beth} and Milne, {Roger L.} and Goldgar, {David E.} and Rookus, {Matti A.} and Nadine Andrieu and Easton, {Douglas F.} and {on behalf of IBCCS, kConFab and BCFR}",

year = "2020",

month = jan,

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doi = "10.1186/s13058-020-1247-4",

language = "English",

volume = "22",

journal = "Breast Cancer Research",

issn = "1465-542X",

publisher = "BioMed Central",

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Mavaddat, N, Antoniou, AC, Mooij, TM, Hooning, MJ, Heemskerk-Gerritsen, BA, Noguès, C, Gauthier-Villars, M, Caron, O, Gesta, P, Pujol, P, Lortholary, A, Barrowdale, D, Frost, D, Evans, DG, Izatt, L, Adlard, J, Eeles, R, Brewer, C, Tischkowitz, M, Henderson, A, Cook, J, Eccles, D, van Engelen, K, Mourits, MJE, Ausems, MGEM, Koppert, LB, Hopper, JL, John, EM, Chung, WK, Andrulis, IL, Daly, MB, Buys, SS, Benitez, J, Caldes, T, Jakubowska, A, Simard, J, Singer, CF, Tan, Y, Olah, E, Navratilova, M, Foretova, L, Gerdes, AM, Roos-Blom, MJ, Van Leeuwen, FE, Arver, B, Olsson, H, Schmutzler, RK, Engel, C, Kast, K, Phillips, KA, Terry, MB, Milne, RL, Goldgar, DE, Rookus, MA, Andrieu, N, Easton, DF & on behalf of IBCCS, kConFab and BCFR 2020, 'Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers', Breast Cancer Research, vol. 22, no. 1, 8. https://doi.org/10.1186/s13058-020-1247-4

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 - Terry, Mary Beth

AU - Milne, Roger L.

AU - Goldgar, David E.

AU - Rookus, Matti A.

AU - Andrieu, Nadine

AU - Easton, Douglas F.

AU - on behalf of IBCCS, kConFab and BCFR

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 - Article

C2 - 31948486

AN - SCOPUS:85078031432

SN - 1465-542X

VL - 22

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

M1 - 8

ER -

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

Abstract

Keywords

UN SDGs

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Erratum: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: An international prospective cohort of BRCA1 and BRCA2 mutation carriers (Breast Cancer Res (2020) 22 (8) DOI: 10.1186/s13058-020-1247-4)

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