Infertility, ovulation-induction treatments and the incidence of breast cancer – a historical prospective cohort in Israeli women

Background: Infertility treatments may be associated with increased breast cancer risk. Results so far have been inconclusive. Objective: To evaluate the association between infertility, infertility treatments and breast cancer risk. Methods: A historical prospective cohort with 5,788 women who attended 5 Israeli infertility centers between 1964 and 1984. Their medical charts were abstracted. Breast cancer incidence was determined through linkage with the National Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing observed cancer rates to those expected in the general population. Additionally, in order to control for known risk factors, a casecontrol study nested within the cohort was carried out as well based on telephone interviews with breast cancer cases and controls matched by 1:2 ratio. Results: Compared to 115.2 expected breast cancer cases, 131 were observed (SIR = 1.1;non-significant). Risk for breast cancer was higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0–1.8). Similar results were noted when treated and untreated women were compared, and when multivariate models were applied. In the nested case-control study, higher cycle index and treatment with clomiphene citrate were associated with significantly higher risk for breast cancer. Conclusions: Clomiphene citrate may be associated with higher breast cancer risk.