title: Breast cancer risk associated with ovulation-stimulating drugs.
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 > or = 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. brinton@nih.gov
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Bert
authors.initials: B
authors.lastname: Scoccia
authors.forename: Kamran S
authors.initials: KS
authors.lastname: Moghissi
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Althuis
authors.forename: Jerome E
authors.initials: JE
authors.lastname: Mabie
authors.forename: Emmet J
authors.initials: EJ
authors.lastname: Lamb
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000473:pathology; D002996:Clomiphene / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006062:Gonadotropins / Q000009:adverse effects*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy*; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D010062:Ovulation Induction / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D006062:Gonadotropins; D002996:Clomiphene