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

EMBRACE, GENEPSO, BCFR, HEBON, kConFab, IBCCS, 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., Berthet, P., Bonadona, V. E., Leroux, D., Mouret-Fourme, E., Venat-Bouvet, L., Buys, S. S., Southey, M. C., John, E. M., Chung, W. K., Daly, M. B., Bane, A., van Asperen, C. J., Garcia, E. B. G., Mourits, M. J., Roos-Blom, M-J., Friedlander, M. L., McLachlan, S-A., Singer, C. F. & van Leeuwen, F. E., Apr-2018, In : JNCI cancer spectrum. 2, 2, 14 p., pky023.

Research output: Contribution to journalArticleAcademicpeer-review

  • BCFR
  • kConFab
  • 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
  • M. J. Mourits
  • Marie-Jose Roos-Blom
  • Michael L. Friedlander
  • Sue-Anne McLachlan
  • Christian F. Singer
  • F. E. van Leeuwen

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 languageEnglish
Article numberpky023
Number of pages14
JournalJNCI cancer spectrum
Issue number2
Publication statusPublished - Apr-2018



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