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.