(HealthDay News) — Women with ever use of clomiphene have no increased breast cancer risk, although women undergoing multiple clomiphene cycles have an increased risk of invasive breast cancer, according to a study published online April 3 in Cancer Epidemiology, Biomarkers & Prevention.

Louise A. Brinton, PhD, MPH, from the National Cancer Institute in Rockville, MD, and colleagues conducted extended follow-up in a cohort of 12,193 women evaluated for infertility between 1965 and 1988. A total of 9,892 women were followed through 2010 via passive and active (questionnaire) means to examine the impact of fertility drugs on breast cancer risk.

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The researchers observed 749 breast cancers during 30.0 median years of follow-up (285,332 person-years).

Breast cancer risk was not associated with ever use of clomiphene citrate (among 38.1% of patients; hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90 to 1.22). Patients who received multiple cycles had somewhat higher risks, with a significant elevation in the risk of medical record-confirmed invasive cancers (HR, 1.69; 95% CI, 1.17 to 2.46). After adjustment for causes of infertility and multiple breast cancer predictors, the risk remained relatively unchanged.

An inconsistent correlation with risk was seen for use of gonadotropins (used by 9.6% of patients, mainly in conjunction with clomiphene). For women who remained nulligravid, the correlation of use with invasive cancers was significantly increased (HR, 1.98; 95 percent CI, 1.04 to 3.60).

“Given our focus on a relatively young population, additional evaluation of long-term fertility drug effects on breast cancer is warranted,” the researchers wrote.

One researcher disclosed financial ties to the pharmaceutical industry.


  1. Brinton LA, Scoccia B, Moghissi KS, et al. Long-term Relationship of Ovulation-Stimulating Drugs to Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2014; doi:10.1158/1055-9965.EPI-13-0996.