Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Lieske H. Schrijver; Hakan Olsson; Kelly-Anne Phillips; Mary Beth Terry; David E. Goldgar; Karin Kast; Christoph Engel; Thea M. Mooij; Julian Adlard; Daniel Barrowdale; Rosemarie Davidson; Ros Eeles; Steve Ellis; D. Gareth Evans; Debra Frost; Louise Izatt; Mary E. Porteous; Lucy E. Side; Lisa Walker; Pascaline Berthet; Val Erie Bonadona; Dominique Leroux; Emmanuelle Mouret-Fourme; Laurence Venat-Bouvet; Saundra S. Buys; Melissa C. Southey; Esther M. John; Wendy K. Chung; Mary B. Daly; Anita Bane; Christi J. van Asperen; Encarna B. Gomez Garcia; Marian J. E. Mourits; Marie-Jose Roos-Blom; Michael L. Friedlander; Sue-Anne McLachlan; Christian F. Singer; Lenka Foretova; Anne-Marie Gerdes; Trinidad Caldes; Edith Olah; Anna Jakubowska; Catherine Nogues; Nadine Andrieu; F. E. van Leeuwen; M. K. Schmidt; R. Wijnands; M. G. E. M. Ausems; M. J. Blok; EMBRACE; GENEPSO; Breast Cancer Family Registry (BCFR); HEBON; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); IBCCS; Matti A. Rookus

doi:10.1093/jncics/pky023

Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Lieske H. Schrijver, Hakan Olsson, Kelly-Anne Phillips, Mary Beth Terry, David E. Goldgar, Karin Kast, Christoph Engel, Thea M. Mooij, Julian Adlard, Daniel Barrowdale, Rosemarie Davidson, Ros Eeles, Steve Ellis, D. Gareth Evans, Debra Frost, Louise Izatt, Mary E. Porteous, Lucy E. Side, Lisa Walker, Pascaline BerthetVal Erie Bonadona, Dominique Leroux, Emmanuelle Mouret-Fourme, Laurence Venat-Bouvet, Saundra S. Buys, Melissa C. Southey, Esther M. John, Wendy K. Chung, Mary B. Daly, Anita Bane, Christi J. van Asperen, Encarna B. Gomez Garcia, Marian J. E. Mourits, Marie-Jose Roos-Blom, Michael L. Friedlander, Sue-Anne McLachlan, Christian F. Singer, Lenka Foretova, Anne-Marie Gerdes, Trinidad Caldes, Edith Olah, Anna Jakubowska, Catherine Nogues, Nadine Andrieu, F. E. van Leeuwen, M. K. Schmidt, R. Wijnands, M. G. E. M. Ausems, M. J. Blok, EMBRACE, GENEPSO, Breast Cancer Family Registry (BCFR), HEBON, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), IBCCS, Matti A. Rookus^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.

Methods: Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.

Results: For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P <.001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).

Conclusions: Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40-50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and non-hormonal contraceptive methods should be discussed.

Original language	English
Article number	023
Number of pages	14
Journal	JNCI Cancer Spectrum
Volume	2
Issue number	2
DOIs	https://doi.org/10.1093/jncics/pky023
Publication status	Published - Apr 2018

Keywords

OVARIAN-CANCER
WOMEN
CONSORTIUM
PREVENTION
KCONFAB

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Schrijver, L. H., Olsson, H., Phillips, K.-A., Terry, M. B., Goldgar, D. E., Kast, K., Engel, C., Mooij, T. M., Adlard, J., Barrowdale, D., Davidson, R., Eeles, R., Ellis, S., Evans, D. G., Frost, D., Izatt, L., Porteous, M. E., Side, L. E., Walker, L., ... Rookus, M. A. (2018). Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study. JNCI Cancer Spectrum, 2(2), Article 023. https://doi.org/10.1093/jncics/pky023

@article{d29ceb3c8f4c4a63bf8d7e536bc1ac65,

title = "Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study",

abstract = "Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.Methods: Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.Results: For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P <.001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).Conclusions: Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40-50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and non-hormonal contraceptive methods should be discussed.",

keywords = "OVARIAN-CANCER, WOMEN, CONSORTIUM, PREVENTION, KCONFAB",

author = "Schrijver, {Lieske H.} and Hakan Olsson and Kelly-Anne Phillips and Terry, {Mary Beth} and Goldgar, {David E.} and Karin Kast and Christoph Engel and Mooij, {Thea M.} and Julian Adlard and Daniel Barrowdale and Rosemarie Davidson and Ros Eeles and Steve Ellis and Evans, {D. Gareth} and Debra Frost and Louise Izatt and Porteous, {Mary E.} and Side, {Lucy E.} and Lisa Walker and Pascaline Berthet and Bonadona, {Val Erie} and Dominique Leroux and Emmanuelle Mouret-Fourme and Laurence Venat-Bouvet and Buys, {Saundra S.} and Southey, {Melissa C.} and John, {Esther M.} and Chung, {Wendy K.} and Daly, {Mary B.} and Anita Bane and {van Asperen}, {Christi J.} and Garcia, {Encarna B. Gomez} and Mourits, {Marian J. E.} and Marie-Jose Roos-Blom and Friedlander, {Michael L.} and Sue-Anne McLachlan and Singer, {Christian F.} and Lenka Foretova and Anne-Marie Gerdes and Trinidad Caldes and Edith Olah and Anna Jakubowska and Catherine Nogues and Nadine Andrieu and {van Leeuwen}, {F. E.} and Schmidt, {M. K.} and R. Wijnands and Ausems, {M. G. E. M.} and Blok, {M. J.} and EMBRACE and GENEPSO and {Breast Cancer Family Registry (BCFR)} and HEBON and {Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)} and IBCCS and Rookus, {Matti A.}",

year = "2018",

month = apr,

doi = "10.1093/jncics/pky023",

language = "English",

volume = "2",

journal = "JNCI Cancer Spectrum",

issn = "1475-4029",

publisher = "Oxford University Press",

number = "2",

}

Schrijver, LH, Olsson, H, Phillips, K-A, Terry, MB, Goldgar, DE, Kast, K, Engel, C, Mooij, TM, Adlard, J, Barrowdale, D, Davidson, R, Eeles, R, Ellis, S, Evans, DG, Frost, D, Izatt, L, Porteous, ME, Side, LE, Walker, L, Berthet, P, Bonadona, VE, Leroux, D, Mouret-Fourme, E, Venat-Bouvet, L, Buys, SS, Southey, MC, John, EM, Chung, WK, Daly, MB, Bane, A, van Asperen, CJ, Garcia, EBG, Mourits, MJE, Roos-Blom, M-J, Friedlander, ML, McLachlan, S-A, Singer, CF, Foretova, L, Gerdes, A-M, Caldes, T, Olah, E, Jakubowska, A, Nogues, C, Andrieu, N, van Leeuwen, FE, Schmidt, MK, Wijnands, R, Ausems, MGEM, Blok, MJ, EMBRACE, GENEPSO, Breast Cancer Family Registry (BCFR), HEBON, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), IBCCS & Rookus, MA 2018, 'Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study', JNCI Cancer Spectrum, vol. 2, no. 2, 023. https://doi.org/10.1093/jncics/pky023

TY - JOUR

T1 - Oral Contraceptive Use and Breast Cancer Risk

T2 - Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

AU - Schrijver, Lieske H.

AU - Olsson, Hakan

AU - Phillips, Kelly-Anne

AU - Terry, Mary Beth

AU - Goldgar, David E.

AU - Kast, Karin

AU - Engel, Christoph

AU - Mooij, Thea M.

AU - Adlard, Julian

AU - Barrowdale, Daniel

AU - Davidson, Rosemarie

AU - Eeles, Ros

AU - Ellis, Steve

AU - Evans, D. Gareth

AU - Frost, Debra

AU - Izatt, Louise

AU - Porteous, Mary E.

AU - Side, Lucy E.

AU - Walker, Lisa

AU - Berthet, Pascaline

AU - Bonadona, Val Erie

AU - Leroux, Dominique

AU - Mouret-Fourme, Emmanuelle

AU - Venat-Bouvet, Laurence

AU - Buys, Saundra S.

AU - Southey, Melissa C.

AU - John, Esther M.

AU - Chung, Wendy K.

AU - Daly, Mary B.

AU - Bane, Anita

AU - van Asperen, Christi J.

AU - Garcia, Encarna B. Gomez

AU - Mourits, Marian J. E.

AU - Roos-Blom, Marie-Jose

AU - Friedlander, Michael L.

AU - McLachlan, Sue-Anne

AU - Singer, Christian F.

AU - Foretova, Lenka

AU - Gerdes, Anne-Marie

AU - Caldes, Trinidad

AU - Olah, Edith

AU - Jakubowska, Anna

AU - Nogues, Catherine

AU - Andrieu, Nadine

AU - van Leeuwen, F. E.

AU - Schmidt, M. K.

AU - Wijnands, R.

AU - Ausems, M. G. E. M.

AU - Blok, M. J.

AU - EMBRACE

AU - GENEPSO

AU - Breast Cancer Family Registry (BCFR)

AU - HEBON

AU - Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

AU - IBCCS

AU - Rookus, Matti A.

PY - 2018/4

Y1 - 2018/4

N2 - Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.Methods: Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.Results: For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P <.001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).Conclusions: Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40-50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and non-hormonal contraceptive methods should be discussed.

AB - Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.Methods: Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.Results: For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P <.001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).Conclusions: Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40-50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and non-hormonal contraceptive methods should be discussed.

KW - OVARIAN-CANCER

KW - WOMEN

KW - CONSORTIUM

KW - PREVENTION

KW - KCONFAB

U2 - 10.1093/jncics/pky023

DO - 10.1093/jncics/pky023

M3 - Article

C2 - 31360853

SN - 1475-4029

VL - 2

JO - JNCI Cancer Spectrum

JF - JNCI Cancer Spectrum

IS - 2

M1 - 023

ER -

Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

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