Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2.

Phillips, K-A; Kotsopoulos, J; Domchek, SM; Terry, MB; Chamberlain, JA; Bassett, JK; Aeilts, AM; Andrulis, IL; Buys, SS; Cui, W; Daly, MB; Eisen, AF; Foulkes, WD; Friedlander, ML; Gronwald, J; Hopper, JL; John, EM; Karlan, BY; Kim, RH; Kurian, AW; Lubinski, J; Metcalfe, K; Nathanson, KL; Singer, CF; Southey, MC; Symecko, H; Tung, N; Narod, SA; Milne, RL; Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry, and the Breast Cancer Family Registry,; Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry and the Breast Cancer Family Registry,

Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2.

Phillips, K-A Kotsopoulos, J Domchek, SM Terry, MB Chamberlain, JA Bassett, JK Aeilts, AM Andrulis, IL Buys, SS Cui, W Daly, MB Eisen, AF Foulkes, WD Friedlander, ML Gronwald, J Hopper, JL John, EM Karlan, BY Kim, RH Kurian, AW Lubinski, J Metcalfe, K Nathanson, KL Singer, CF Southey, MC Symecko, H Tung, N Narod, SA Milne, RL Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry, and the Breast Cancer Family Registry, Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry and the Breast Cancer Family Registry,

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Publisher:: American Society of Clinical Oncology (ASCO)
Publication Type:: Journal Article
Citation:: J Clin Oncol, 2025, 43, (4), pp. 422-431
Issue Date:: 2025-02

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Field	Value	Language
dc.contributor.author	Phillips, K-A
dc.contributor.author	Kotsopoulos, J
dc.contributor.author	Domchek, SM
dc.contributor.author	Terry, MB
dc.contributor.author	Chamberlain, JA
dc.contributor.author	Bassett, JK
dc.contributor.author	Aeilts, AM
dc.contributor.author	Andrulis, IL
dc.contributor.author	Buys, SS
dc.contributor.author	Cui, W
dc.contributor.author	Daly, MB
dc.contributor.author	Eisen, AF
dc.contributor.author	Foulkes, WD
dc.contributor.author	Friedlander, ML
dc.contributor.author	Gronwald, J
dc.contributor.author	Hopper, JL
dc.contributor.author	John, EM
dc.contributor.author	Karlan, BY
dc.contributor.author	Kim, RH
dc.contributor.author	Kurian, AW
dc.contributor.author	Lubinski, J
dc.contributor.author	Metcalfe, K
dc.contributor.author	Nathanson, KL
dc.contributor.author	Singer, CF
dc.contributor.author	Southey, MC
dc.contributor.author	Symecko, H
dc.contributor.author	Tung, N
dc.contributor.author	Narod, SA
dc.contributor.author	Milne, RL
dc.contributor.author	Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry, and the Breast Cancer Family Registry,
dc.contributor.author	Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry and the Breast Cancer Family Registry,
dc.date.accessioned	2025-02-27T03:22:11Z
dc.date.available	2025-02-27T03:22:11Z
dc.date.issued	2025-02
dc.identifier.citation	J Clin Oncol, 2025, 43, (4), pp. 422-431
dc.identifier.issn	0732-183X
dc.identifier.issn	1527-7755
dc.identifier.uri	http://hdl.handle.net/10453/185379
dc.description.abstract	PURPOSE: It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers. METHODS: Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression. RESULTS: Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively). CONCLUSION: Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	American Society of Clinical Oncology (ASCO)
dc.relation.ispartof	J Clin Oncol
dc.relation.isbasedon	10.1200/JCO.24.00176
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.subject.classification	3211 Oncology and carcinogenesis
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Germ-Line Mutation
dc.subject.mesh	Adult
dc.subject.mesh	Middle Aged
dc.subject.mesh	Prospective Studies
dc.subject.mesh	BRCA1 Protein
dc.subject.mesh	BRCA2 Protein
dc.subject.mesh	Hormonal Contraception
dc.subject.mesh	Heterozygote
dc.subject.mesh	Genes, BRCA2
dc.subject.mesh	Genes, BRCA1
dc.subject.mesh	Risk Factors
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	BRCA1 Protein
dc.subject.mesh	BRCA2 Protein
dc.subject.mesh	Risk Factors
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Heterozygote
dc.subject.mesh	Germ-Line Mutation
dc.subject.mesh	Genes, BRCA1
dc.subject.mesh	Genes, BRCA2
dc.subject.mesh	Adult
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Hormonal Contraception
dc.title	Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2.
dc.type	Journal Article
utslib.citation.volume	43
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2025-02-27T03:22:08Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	43
utslib.citation.issue	4

Abstract:

PURPOSE: It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers. METHODS: Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression. RESULTS: Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively). CONCLUSION: Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.

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