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Hum. Reprod. Advance Access published online on June 24, 2004
Human Reproduction, doi:10.1093/humrep/deh371
© 2004 by European Society of Human Reproduction and Embryology
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Received March 15, 2004
Accepted May 5, 2004

Article

Breast cancer risk associated with ovulation-stimulating drugs

Louise A. Brinton 1*, Bert Scoccia 2, Kamran S. Moghissi 3, Carolyn L. Westhoff 4, Michelle D. Althuis 1, Jerome E. Mabie 5, Emmet J. Lamb 6

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
2 University of Illinois, Chicago, IL, USA
3 Wayne State University, Detroit, MI, USA
4 Columbia University, New York, NY, USA
5 Information Management Services, Inc., Rockville, MD, USA
6 Stanford University, Stanford, CA, USA

* To whom correspondence should be addressed. E-mail: brinton{at}nih.gov.


  Abstract

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12 193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after ≥20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.

Keywords: breast cancer; epidemiology; infertility; ovulation-stimulating medications; risk.
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