Risk of breast cancer after exposure to fertility drugs: Results from a large Danish cohort study

Background: Few epidemiologic studies have examined the association between fertility drugs and breast cancer risk, and results have been contradicting. Using data from the largest cohort of infertile women to date, the aim of this study was to examine the effects of fertility drugs on breast cancer risk overall and according to histologic subtypes. Method: A cohort of 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998 was established. A detailed data collection, including information of type and amount of treatment, was conducted. We used case-cohort techniques to calculate rate ratios (RR) of breast cancer associated with use of five groups of fertility drugs, after adjustment for parity status. Results: Three hundred thirty-one invasive breast cancers were identified in the cohort during follow-up through 1998. Analyses within cohort showed no overall increased breast cancer risk after use of gonadotrophins, clomiphene, human chorionic gonadotrophin, or gonadotrophin-releasing hormone, whereas use of progesterone increased breast cancer risk (RR, 3.36; 95% confidence interval, 1.3-8.6). For all groups of fertility drugs, no relationships with number of cycles of use or years since first use of fertility drug were found. However, gonadotrophins may have a stronger effect on breast cancer risk among nulliparous women (RR, 1.69; 95% confidence interval, 1.03-2.77). Similar risk patterns were present for ductal, lobular, and tumors of other histologies, indicating identical etiologies. Conclusion: The results showed no strong association between breast cancer risk and use of fertility drugs. Follow-up is, however, needed to assess long-term breast cancer risk after use of progesterone and among nulliparous women exposed to gonadotrophins.