Skip to main content

Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review

Abstract

Purpose

BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers.

Methods

We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library.

Results

We included four meta-analyses, one review, one case–control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case–control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC.

Conclusion

Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips K-A, Mooij TM, Roos-Blom M-J et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F et al (2016) Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol 27(suppl 5):v103–v110

    CAS  PubMed  Google Scholar 

  3. 3.

    Mørch LS, Hannaford PC, Lidegaard Ø (2018) Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 378(13):1265–1266

    PubMed  Google Scholar 

  4. 4.

    Beral V, Doll R, Hermon C, Peto R, Reeves G (2008) Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 371(9609):303–314

    CAS  PubMed  Google Scholar 

  5. 5.

    Narod SA, Risch H, Moslehi R, Dørum A, Neuhausen S, Olsson H et al (1998) Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 339(7):424–428

    CAS  PubMed  Google Scholar 

  6. 6.

    Iodice S, Barile M, Rotmensz N, Feroce I, Bonanni B, Radice P et al (2010) Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer 46(12):2275–2284

    CAS  PubMed  Google Scholar 

  7. 7.

    Whittemore AS, Balise RR, Pharoah PDP, Dicioccio RA, Oakley-Girvan I, Ramus SJ et al (2004) Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 91(11):1911–1915

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Antoniou AC, Rookus M, Andrieu N, Brohet R, Chang-Claude J, Peock S et al (2009) Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 18(2):601–610

    CAS  PubMed  Google Scholar 

  9. 9.

    Runnebaum IB, Wang-Gohrke S, Vesprini D, Kreienberg R, Lynch H, Moslehi R et al (2001) Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics 11(7):635–638

    CAS  PubMed  Google Scholar 

  10. 10.

    McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H et al (2007) Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case–control study. Lancet Oncol 8(1):26–34

    CAS  PubMed  Google Scholar 

  11. 11.

    Cibula D, Gompel A, Mueck AO, La Vecchia C, Hannaford PC, Skouby SO et al (2010) Hormonal contraception and risk of cancer. Hum Reprod Update 16(6):631–650

    CAS  PubMed  Google Scholar 

  12. 12.

    Modan B, Hartge P, Hirsh-Yechezkel G, Chetrit A, Lubin F, Beller U et al (2001) Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 345(4):235–240

    CAS  PubMed  Google Scholar 

  13. 13.

    Cibula D, Zikan M, Dusek L, Majek O (2011) Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Rev Anticancer Ther 11(8):1197–1207

    CAS  PubMed  Google Scholar 

  14. 14.

    Gronwald J, Byrski T, Huzarski T, Cybulski C, Sun P, Tulman A et al (2006) Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat 95(2):105–109

    PubMed  Google Scholar 

  15. 15.

    Moorman PG, Havrilesky LJ, Gierisch JM, Coeytaux RR, Lowery WJ, Peragallo Urrutia R et al (2013) Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol 31(33):4188–4198

    CAS  PubMed  Google Scholar 

  16. 16.

    Friebel TM, Domchek SM, Rebbeck TR (2014) Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju091

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Narod SA, Sun P, Ghadirian P, Lynch H, Isaacs C, Garber J et al (2001) Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case–control study. Lancet 357(9267):1467–1470

    CAS  PubMed  Google Scholar 

  18. 18.

    Vicus D, Rosen B, Lubinski J, Domchek S, Kauff ND, Lynch HT et al (2009) Tamoxifen and the risk of ovarian cancer in BRCA1 mutation carriers. Gynecol Oncol 115(1):135–137

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Perri T, Lifshitz D, Sadetzki S, Oberman B, Meirow D, Ben-Baruch G et al (2015) Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers. Fertil Steril 103(5):1305–1312

    PubMed  Google Scholar 

  20. 20.

    Pasanisi P, Hédelin G, Berrino J, Chang-Claude J, Hermann S, Steel M et al (2009) Oral contraceptive use and BRCA penetrance: a case-only study. Cancer Epidemiol Biomarkers Prev 18(7):2107–2113

    CAS  PubMed  Google Scholar 

  21. 21.

    Heimdal K, Skovlund E, Møller P (2002) Oral contraceptives and risk of familial breast cancer. Cancer Detect Prev 26(1):23–27

    CAS  PubMed  Google Scholar 

  22. 22.

    Jernström H, Loman N, Johannsson OT, Borg A, Olsson H (2005) Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing. Eur J Cancer 41(15):2312–2320

    PubMed  Google Scholar 

  23. 23.

    Sade RBB, Chetrit A, Figer A, Papa MZ, Flex D, Rizel S et al (2006) Hormone replacement therapy is more prevalent among Jewish BRCA1/2 mutation carriers. Eur J Cancer 42(5):650–655

    CAS  PubMed  Google Scholar 

  24. 24.

    Ursin G, Henderson BE, Haile RW, Pike MC, Zhou N, Diep A et al (1997) Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women? Cancer Res 57(17):3678–3681

    CAS  PubMed  Google Scholar 

  25. 25.

    Narod SA, Dubé M-P, Klijn J, Lubinski J, Lynch HT, Ghadirian P et al (2002) Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 94(23):1773–1779

    CAS  PubMed  Google Scholar 

  26. 26.

    Brohet RM, Goldgar DE, Easton DF, Antoniou AC, Andrieu N, Chang-Claude J et al (2007) Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 25(25):3831–3836

    PubMed  Google Scholar 

  27. 27.

    Milne RL, Knight JA, John EM, Dite GS, Balbuena R, Ziogas A et al (2005) Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 14(2):350–356

    CAS  PubMed  Google Scholar 

  28. 28.

    Haile RW, Thomas DC, McGuire V, Felberg A, John EM, Milne RL et al (2006) BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 15(10):1863–1870

    CAS  PubMed  Google Scholar 

  29. 29.

    Bernholtz S, Laitman Y, Kaufman B, Paluch Shimon S, Friedman E (2011) Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: effects of oral contraceptive use and parental origin of mutation. Breast Cancer Res Treat 129(2):557–563

    CAS  PubMed  Google Scholar 

  30. 30.

    Kotsopoulos J, Lubinski J, Moller P, Lynch HT, Singer CF, Eng C et al (2014) Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers. Breast Cancer Res Treat 143(3):579–586

    CAS  PubMed  Google Scholar 

  31. 31.

    Gronwald J, Glass K, Rosen B, Karlan B, Tung N, Neuhausen SL et al (2016) Treatment of infertility does not increase the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation. Fertil Steril 105(3):781–785

    CAS  PubMed  Google Scholar 

  32. 32.

    Kotsopoulos J, Lubinski J, Lynch HT, Kim-Sing C, Neuhausen S, Demsky R et al (2012) Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 21(7):1089–1096

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Rieder V, Salama M, Glöckner L, Muhr D, Berger A, Tea M-K et al (2016) Effect of lifestyle and reproductive factors on the onset of breast cancer in female BRCA 1 and 2 mutation carriers. Mol Genet Genomic Med 4(2):172–177

    CAS  PubMed  Google Scholar 

  34. 34.

    Park B, Hopper JL, Win AK, Dowty JG, Sung HK, Ahn C et al (2017) Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers. Oncotarget 8(60):102110–102118

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Schrijver LH, Olsson H, Phillips K-A, Terry MB, Goldgar DE, Kast K et al (2018) Oral contraceptive use and breast cancer risk: retrospective and prospective analyses from a BRCA1 and BRCA2 mutation carrier cohort study. JNCI Cancer Spectr 2(2):pky023

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Antoniou AC, Goldgar DE, Andrieu N, Chang-Claude J, Brohet R, Rookus MA et al (2005) A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes. Genet Epidemiol 29(1):1–11

    PubMed  Google Scholar 

  38. 38.

    McGuire V, Felberg A, Mills M, Ostrow KL, DiCioccio R, John EM et al (2004) Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations. Am J Epidemiol 160(7):613–618

    CAS  PubMed  Google Scholar 

  39. 39.

    Jernström H, Lerman C, Ghadirian P, Lynch HT, Weber B, Garber J et al (1999) Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. Lancet 354(9193):1846–1850

    PubMed  Google Scholar 

  40. 40.

    Lee E, Ma H, McKean-Cowdin R, van den Berg D, Bernstein L, Henderson BE et al (2008) Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev 17(11):3170–3178

    CAS  PubMed  Google Scholar 

  41. 41.

    Figueiredo JC, Haile RW, Bernstein L, Malone KE, Largent J, Langholz B et al (2010) Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study. Breast Cancer Res Treat 120(1):175–183

    CAS  PubMed  Google Scholar 

  42. 42.

    Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM et al (2008) Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol 26(26):4282–4288

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

DH: Literature search, data analysis, manuscript writing. SS: Data analysis, manuscript writing. KK, GE: Manuscript editing. OO: Project development, manuscript editing.

Corresponding author

Correspondence to O. Ortmann.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huber, D., Seitz, S., Kast, K. et al. Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. Arch Gynecol Obstet 301, 875–884 (2020). https://doi.org/10.1007/s00404-020-05458-w

Download citation

Keywords

  • Oral contraception
  • Breast cancer
  • Ovarian cancer
  • BRCA1
  • BRCA2