Oral contraceptive use and breast cancer risk: retrospective and prospective analyses from a BRCA1 and BRCA2 mutation carrier cohort study

Schrijver, L.H.; Olsson, H.; Phillips, K.A.; Terry, M.B.; Goldgar, D.E.; Kast, K.; ... ; IBCCS (2018)

Article / Letter to editor

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.

• All authors: 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.; Asperen, C.J. van; Garcia, E.B.G.; Mourits, M.J.E.; Roos-Blom, M.J.; Friedlander, M.L.; McLachlan, S.A.; Singer, C.F.; Foretova, L.; Gerdes, A.M.; Caldes, T.; Olah, E.; Jakubowska, A.; Nogues, C.; Andrieu, N.; Easton, D.F.; Leeuwen, F.E. van; Hopper, J.L.; Milne, R.L.; Antoniou, A.C.; Rookus, M.A.; Hogervorst, F.B.L.; Adank, M.A.; Schmidt, M.K.; Russell, N.S.; Lange, J.L. de; Wijnands, R.; Jenner, D.J.; Collee, J.M.; Ouweland, A.M.W. van den; Hooning, M.J.; Seynaeve, C.; Deurzen, C.H.M. van; Obdeijn, I.M.; Wijnen, J.T.; Tollenaar, R.A.E.M.; Devilee, P.; Cronenburg, T.C.T.E.F. van; Kets, C.M.; Mensenkamp, A.R.; Ausems, M.G.E.M.; Luijt, R.B. van der; Pol, C.C. van der; Aalfs, C.M.; Meijers-Heijboer, H.E.J.; Os, T.A.M. van; Engelen, K. van; Gille, J.J.P.; Waisfisz, Q.; Gomez-Garcia, E.B.; Blok, M.J.; Oosterwijk, J.C.; Hout, A.H. van der; Mourits, M.J.; Bock, G.H. de; Siesling, S.; Verloop, J.; Overbeek, L.I.H.; EMBRACE; GENEPSO; BCFR; HEBON; KConFab; IBCCS
• Date: 2018-04-01
• Journal: JNCI Cancer Spectrum
• Volume: 2
• Issue: 2
• DOI: doi:10.1093/jncics/pky023
• Link: https://academic.oup.com/jncics/article/2/2/pky023/5046628