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Long-Term Study Finds Fertility Drugs Do Not Increase Breast Cancer Risk

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Key Points

  • In a long-term study of 12,000 women, those who took clomiphene citrate or gonadotropins for infertility did not have an increased risk of breast cancer compared to those who did not receive those medications.
  • An elevated risk for invasive breast cancer was observed for a small number of women who took 12 or more cycles of clomiphene.
  • Women who remained unable to conceive after taking gonadotropins and clomiphene citrate had nearly twice the risk of women in the study who never took either medication.

A large study of over 12,000 women who took clomiphene citrate or gonadotropins for the treatment of infertility has found no increase in breast cancer risk over 30 years of follow-up, compared with women who were not treated with these medications. The study by Brinton et al is published in Cancer Epidemiology, Biomarkers & Prevention.

Study Details

The researchers analyzed medical record data from a cohort of 12,193 women who had sought infertility advice between 1965 and 1988 at five different reproductive practices throughout the United States. The patients were followed until 2010, and 9,892 were eligible for this study.

The follow-up procedure included searches for deaths through publically available databases and medical information provided from a questionnaire. The questionnaire focused on the development of cancers and cancer risk factors that might have changed over time, such as reproductive and menopausal status.

In addition to information on cancers identified through death records and the completed questionnaires, the researchers made use of cancer registries in the 14 states where the majority of the patients lived. Cox regression analysis determined hazard ratios (HR) and 95% confidence intervals (CI) for fertility treatments adjusted for breast cancer risk factors and causes of infertility.

Results

During the median 30 years of follow-up, 749 breast cancers were observed. "Ever use" of clomiphene citrate among 38.1% of patients was not associated with increased risk of breast cancer (HR = 1.05, 95% CI = 0.90–1.22 vs "never use"). A somewhat higher risk, however, was seen for women who received multiple cycles of the drug, with the risk for invasive cancers confirmed by medical records being significantly elevated (HR = 1.69, 95% CI = 1.17–2.46). This risk remained relatively unchanged after adjusting for causes of infertility and multiple breast cancer predictors.

Gonadotropins, used by 9.6% of the patients—usually in conjunction with clomiphene—showed inconsistent associations with risk, although a significant relationship of use with invasive cancers was seen among women who remained unable to conceive (HR = 1.98, 95% CI = 1.04–3.60).

“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 use and use of those drugs,” said Louise A. Brinton, PhD, MPH, lead author of the study and Chief of the Hormonal and Reproductive Epidemiology Branch at the National Cancer Institute. “Overall, our data show that use of fertility drugs does not increase breast cancer risk in this population of women, which is reassuring.”

However, “continued monitoring of the long-term effects of these drugs seems warranted, especially given that our study participants were still relatively young (and had not yet reached their peak incidence for breast cancer) and that ovulation-stimulating drugs, including gonadotropins—potent ovulation stimulators (40)—are increasingly being used in infertility treatment protocols,” concluded the study authors.

Dr. Brinton is the corresponding author for the Cancer Epidemiology, Biomarkers & Prevention article.

The study was funded by the National Cancer Institute. Study author Carolyn L. Westhoff, MD, is a consultant/advisory board member of Merck, Bayer, Agile, and Elsevier.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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