Oral contraceptives and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS)

MA Rookus¹, RM Brohet¹, N Andrieu², AC Antoniou³, J Chang-Claude⁴, DF Easton³, S Peock³, C Noguès², FE van Leeuwen¹ and DE Goldgar⁵ for the IBCCS Collaborating Group

¹The Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands

²l'Institut Curie, Paris, France

³Cancer Research UK, University of Cambridge, UK

⁴German Cancer Research Center, Heidelberg, Germany

⁵International Agency for Research on Cancer, Lyon, France

from The Third International Symposium on the Molecular Biology of Breast Cancer
Molde, Norway. 22–26 June 2005

Breast Cancer Research 2005, 7(Suppl 2):P1.10doi:10.1186/bcr1097

Published:

17 June 2005

Background

The marked reduction of the risk of breast cancer following a prophylactic oophorectomy illustrates that endogenous hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers, as they do in the general population. In the general population the use of oral contraceptives has been associated with a slightly increased risk. Little is so far known about the safety of oral contraceptives among BRCA1/2 carriers, who have much higher premenopausal background rates of breast cancer.

Methods

A retrospective cohort study was performed using an international cohort of 1601 BRCA1/2 mutation carriers. A time-dependent proportional hazard Cox regression was used, stratified for birth cohort, gene, country of residence and relatedness. All analyses were adjusted for prophylactic oophorectomy and number of full-term pregnancies. To reduce possible testing bias, the analyses were weighted to achieve the rate of breast cancer within the cohort as a priori estimated for BRCA1/2 mutation carriers.

Results

We found a slightly increased risk of breast cancer for BRCA/12 mutation carriers who ever used oral contraceptives, with an adjusted hazard ratio of 1.47 (95% confidence interval = 1.16-1.87). The risk increase did not vary according to various aspects of oral contraceptive use, such as time since stopping, duration of use, age at start, and calendar year at start. In addition, the risk increase was similar for BRCA1 and BRCA2 mutation carriers.

Conclusion

Use of oral contraceptives seems to be associated with a slightly increased relative risk of breast cancer among BRCA1/2 mutation carriers, comparable with the general population. However, due to the high background rates of breast cancer among BRCA1/2 carriers, oral contraceptive use may result in a considerable absolute excess risk of breast cancer, if the association is causal.

Acknowledgements

This work was supported by NIH Award CA81203, Cancer Research UK, the INHERIT BRCAs research program, the Fondation de France and the Ligue Nationale Contre le Cancer, and the Dutch Cancer Society.

This article is part of the supplement: The Third International Symposium on the Molecular Biology of Breast Cancer