Women who took clomiphene citrate (brand name Clomid) or gonadotropins as a part of fertility treatment did not experience an increased risk for breast cancer over 30 years of follow-up, compared with women who were not treated with these medications, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
"We wanted to evaluate the long-term relationship of fertility medications and breast cancer risk after controlling for other factors that have been shown to be correlated with both breast cancer risk and use of those drugs," said Louise A. Brinton, Ph.D., M.P.H., chief of the Hormonal and Reproductive Epidemiology Branch at the National Cancer Institute (NCI) in Bethesda, Md. "Overall, our data show that use of fertility drugs does not increase breast cancer risk in this population of women, which is reassuring."
An elevated risk for invasive breast cancer was observed for a small number of women who were exposed to 12 or more cycles of clomiphene, who had a little more than 1.5 times the risk of women in the study who never took fertility drugs. Women who were unable to become pregnant after taking gonadotropins and clomiphene citrate had nearly twice the risk of women in the study who never took either medication.
"The observed increase in risk for these small subsets of women may be related to persistent infertility rather than an effect of the medications," said Brinton. "Nevertheless, these findings stress the importance of continued monitoring of women who are exposed to fertility drugs."
Under current practices, clomiphene is usually limited to three to six cycles at doses up to 100 mg, which is far lower than in the past, including patients in this study who were prescribed doses up to 250 mg, oftentimes for many years, explained Brinton.
"Given the high doses of drugs received by our study participants and the lack of large increases in breast cancer risk many years after exposure, women previously exposed to such drugs should be reassured by these findings," said Brinton. "However, the women in our study who developed breast cancer were on average only 53 years old, which is still young in terms of when we usually expect breast cancers to develop.
"This cohort of women should continue to be monitored as they progress into a typical breast cancer age range; in addition, data are needed to assess the long-term effects of fertility drugs given in current practice, such as those used in conjunction with IVF," added Brinton.
This study was conducted using data from a cohort of more than 12,000 women evaluated for infertility between 1965 and 1988 at five different locations in the United States that retained detailed records of infertility evaluations and treatments. These patients were followed until 2010, and 9,892 were eligible for this study. Among them, 749 women developed breast cancer. The researchers were able to obtain medical documentation for 696 of these, and 536 were validated as having invasive breast cancers.
- L. A. Brinton, B. Scoccia, K. S. Moghissi, C. L. Westhoff, S. Niwa, D. Ruggieri, B. Trabert, E. J. Lamb. Long-term Relationship of Ovulation-Stimulating Drugs to Breast Cancer Risk. Cancer Epidemiology Biomarkers & Prevention, 2014; 23 (4): 584 DOI: 10.1158/1055-9965.EPI-13-0996
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