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

Context: Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive. Objective: To evaluate the association between infertility, exposure to ovulation induction drugs and the incidence of breast cancer. Design: Historical prospective cohort and nested case-control study. Setting: Institutional practice Patients: About 5,788 women attending five infertility centers in Israel between 1964 and 1984. Intention: Abstracting of medical records and telephone interviews. Main outcome measure: Breast cancer incidence was determined through linkage with the National Cancer Registry database. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing the observed to the expected cancer rates in the general population. In addition, a nested case-control study within the cohort was performed with interviews of breast cancer cases and two matched controls. Results: The study cohort included 120,895 women years of follow-up. Compared to 115.2 expected breast cancer cases, 131 cases were observed (SIR = 1.1; 95% CI 0.9-1.4). Risk for breast cancer was significantly higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0-1.8). Similar results were noted when comparisons were carried out between treated and untreated women, and when multivariate models were applied. In the nested case-control study, higher cycle index (OR = 2.2; 95% CI 1.0-4.8) and treatment with clomiphene citrate (OR=2.7; 95% CI 1.3-5.7) were associated with higher risk for breast cancer. Conclusion: Infertility and usage of infertility drugs in general are not associated with increased risk for breast cancer. However, for infertile women treated with clomiphene citrate, breast cancer risk is elevated.