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

L. Lerner-Geva, L. Keinan-Boker, T. Blumstein, V. Boyko, L. Olmar, S. Mashiach, J. Rabinovici, G. Potashnik, E. Lunenfeld, J. G. Schenker, A. Shushan, A. Fishman, I. Cohen, I. Vagman, B. Lunenfeld

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Nov 2006

Bibliographical note

Funding Information:
Acknowledgement This work is in partial fulfillment of the requirements of the PhD degree for L. Lerner-Geva, Sackler Faculty of Medicine, Tel Aviv University, Israel. The study was partially supported by the Israel-US bi-national scientific foundation (Grant number 96-269).


  • Breast cancer
  • Clomiphene citrate
  • Infertility
  • Ovulation induction
  • Prospective

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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