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

Schrijver, Lieske H ; Olsson, Håkan LU orcid ; Phillips, Kelly-Anne ; Terry, Mary Beth ; Goldgar, David E ; Kast, Karin ; Engel, Christoph ; Mooij, Thea M ; Adlard, Julian and Barrowdale, Daniel , et al. (2018) In JNCI Cancer Spectrum 2(2).
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... (More)

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 nonhormonal contraceptive methods should be discussed.

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published
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JNCI Cancer Spectrum
volume
2
issue
2
article number
pky023
publisher
Oxford University Press
external identifiers
  • scopus:85071374291
  • pmid:31360853
ISSN
2515-5091
DOI
10.1093/jncics/pky023
language
English
LU publication?
no
id
774b8a1a-6956-4d8e-9462-d0ba634198bb
date added to LUP
2020-01-28 08:42:20
date last changed
2025-10-14 10:39:42
@article{774b8a1a-6956-4d8e-9462-d0ba634198bb,
  abstract     = {{<p>Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.</p><p>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.</p><p>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 &lt; .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).</p><p>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 nonhormonal contraceptive methods should be discussed.</p>}},
  author       = {{Schrijver, Lieske H and Olsson, Håkan and Phillips, Kelly-Anne and Terry, Mary Beth and Goldgar, David E and Kast, Karin and Engel, Christoph and Mooij, Thea M and Adlard, Julian and Barrowdale, Daniel and Davidson, Rosemarie and Eeles, Ros and Ellis, Steve and Evans, D Gareth and Frost, Debra and Izatt, Louise and Porteous, Mary E and Side, Lucy E and Walker, Lisa and Berthet, Pascaline and Bonadona, Valérie and Leroux, Dominique and Mouret-Fourme, Emmanuelle and Venat-Bouvet, Laurence and Buys, Saundra S and Southey, Melissa C and John, Esther M and Chung, Wendy K and Daly, Mary B and Bane, Anita and van Asperen, Christi J and Gómez Garcia, Encarna B and Mourits, Marian J E and van Os, Theo A M and Roos-Blom, Marie-José and Friedlander, Michael L and McLachlan, Sue-Anne and Singer, Christian F and Tan, Yen Y and Foretova, Lenka and Navratilova, Marie and Gerdes, Anne-Marie and Caldes, Trinidad and Simard, Jacques and Olah, Edith and Jakubowska, Anna and Arver, Brita and Osorio, Ana and Noguès, Catherine and Andrieu, Nadine}},
  issn         = {{2515-5091}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{JNCI Cancer Spectrum}},
  title        = {{Oral Contraceptive Use and Breast Cancer Risk : Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study}},
  url          = {{http://dx.doi.org/10.1093/jncics/pky023}},
  doi          = {{10.1093/jncics/pky023}},
  volume       = {{2}},
  year         = {{2018}},
}