Breast Cancer Research and Treatment

, Volume 143, Issue 3, pp 579–586 | Cite as

Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers

  • Joanne Kotsopoulos
  • Jan Lubinski
  • Pal Moller
  • Henry T. Lynch
  • Christian F. Singer
  • Charis Eng
  • Susan L. Neuhausen
  • Beth Karlan
  • Charmaine Kim-Sing
  • Tomasz Huzarski
  • Jacek Gronwald
  • Jeanna McCuaig
  • Leigha Senter
  • Nadine Tung
  • Parviz Ghadirian
  • Andrea Eisen
  • Dawna Gilchrist
  • Joanne L. Blum
  • Dana Zakalik
  • Tuya Pal
  • Ping Sun
  • Steven A. Narod
  • Hereditary Breast Cancer Clinical Study Group


It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case–control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20–1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99–1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14–1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03–1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79–1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.


BRCA1 Oral contraceptives Breast cancer 



Breast cancer susceptibility gene 1


Odds ratios


Confidence interval


Relative risk



We would also like to acknowledge the study coordinators Adriana Valentini, Marcia Llacuachaqui, and Alejandra Ragone, as well as the students and staff Jennifer Ng, Kristi De Buono, Kate Bisnaire, Dina Nikitina, Anneli Loo, Bita Khorram, Dina Gordon, Courtney May, Michelle Jones, Jose Miguel Lozano, who helped with the data collection and data entry. Joanne Kotsopoulos is the recipient of a Cancer Care Ontario Research Chair in Population Studies and a Canadian Cancer Society Career Development Award in Prevention. Charis Eng is the recipient of the Sondra J. and Stephen R. Hardis Chair of Cancer Genomic Medicine at the Cleveland Clinic and of the ACS Clinical Research Professorship. Susan L. Neuhausen is partially supported by the Morris and Horowitz Endowed Professorship and her work was supported by a grant from the NIH, R01CA74415. Tuya Pal’s work is supported by a grant from the Florida Biomedical Research Program, IBG-09. Steven Narod is the recipient of a Canada Research Chair tier I.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Joanne Kotsopoulos
    • 1
  • Jan Lubinski
    • 2
  • Pal Moller
    • 3
  • Henry T. Lynch
    • 4
  • Christian F. Singer
    • 5
  • Charis Eng
    • 6
  • Susan L. Neuhausen
    • 7
  • Beth Karlan
    • 8
  • Charmaine Kim-Sing
    • 9
  • Tomasz Huzarski
    • 2
  • Jacek Gronwald
    • 2
  • Jeanna McCuaig
    • 10
  • Leigha Senter
    • 11
  • Nadine Tung
    • 12
  • Parviz Ghadirian
    • 13
  • Andrea Eisen
    • 14
  • Dawna Gilchrist
    • 15
  • Joanne L. Blum
    • 16
  • Dana Zakalik
    • 17
  • Tuya Pal
    • 18
  • Ping Sun
    • 1
  • Steven A. Narod
    • 1
  • Hereditary Breast Cancer Clinical Study Group
  1. 1.Familial Breast Cancer UnitWomen’s College Research InstituteTorontoCanada
  2. 2.Hereditary Cancer CenterPomeranian Medical UniversitySzczecinPoland
  3. 3.Inherited Cancer Research Group, Department for Medical Genetics, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  4. 4.Department of Preventive Medicine and Public HealthCreighton University School of MedicineOmahaUSA
  5. 5.Department of Obstetrics and Gynecology, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
  6. 6.Center for Personalized Genetic Healthcare, Genomic Medicine InstituteCleveland ClinicClevelandUSA
  7. 7.Department of Population SciencesBeckman Research Institute of City of HopeDuarteUSA
  8. 8.Women’s Cancer Program, Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA
  9. 9.BC Cancer AgencyVancouverCanada
  10. 10.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyUniversity of TorontoTorontoCanada
  11. 11.Division of Human Genetics, Comprehensive Cancer CenterThe Ohio State University Medical CenterColumbusUSA
  12. 12.Beth Israel Deaconess Medical CenterBostonUSA
  13. 13.Epidemiology Research UnitResearch Center of the University of Montreal Hospital Centre (CRCHUM)MontrealCanada
  14. 14.Toronto-Sunnybrook Regional Cancer CenterTorontoCanada
  15. 15.Department of Medicine GeneticsUniversity of AlbertaEdmontonCanada
  16. 16.Hereditary Cancer Risk ProgramBaylor University Medical CenterDallasUSA
  17. 17.Cancer Genetics ProgramBeaumont HospitalRoyal OakUSA
  18. 18.Department of Cancer EpidemiologyMoffitt Cancer CenterTampaUSA

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