title: Fertility drugs and young-onset breast cancer: results from the Two Sister Study.
abstract: BACKGROUND
  Fertility drugs stimulate hyperovulation, which may have implications for breast cancer. We examined the association between use of fertility drugs (clomiphene citrate [CC] and follicle-stimulating hormone [FSH]) and subsequent risk of young-onset (<50 years at diagnosis) breast cancer.
  
  
  METHODS
  We conducted the Two Sister Study, a sister-matched case-control study, by enrolling 1422 women between September 2008 and December 2010, who were younger than age 50 years at diagnosis with breast cancer and were enrolled within 4 years of diagnosis, and 1669 breast cancer-free control sisters from the Sister Study. Participants reported their use of fertility drugs (CC and FSH) and ever-users reported whether a pregnancy had resulted that lasted 10 or more (10+) weeks. Conditional logistic regression was used to estimate confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for fertility drug use with or without conception of a 10+ week pregnancy.
  
  
  RESULTS
  A total of 288 participants reported having used ovulation-stimulating drugs (193 CC only, 29 FSH only, and 66 both). Overall, women who had used fertility drugs showed a non-statistically significantly decreased risk of breast cancer, compared with nonusers (OR = 0.82, 95% CI = 0.63 to 1.08). Women who had used fertility drugs but had not conceived a 10+ week pregnancy under treatment showed a statistically significantly decreased risk of breast cancer compared with nonusers (OR = 0.62, 95% CI = 0.43 to 0.89). Women who had used fertility drugs and conceived a 10+ week pregnancy under treatment showed a statistically significantly increased risk of breast cancer compared with unsuccessfully treated women (OR = 1.82, 95% CI = 1.10 to 3.00), although their risk was not increased compared with women who had not used fertility drugs (OR = 1.13, 95% CI = 0.78 to 1.64).
  
  
  CONCLUSIONS
  In the absence of a 10+ week pregnancy under treatment, exposure to ovulation-stimulating fertility drugs was associated with reduced risk of young-onset breast cancer. This apparent association was absent in women who conceived a 10+ week pregnancy under treatment, for whom risk was higher than that of unsuccessfully treated women, but similar to that of untreated women.
authors: Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: Chunyuan
authors: C
authors: Fei
authors: Lisa A
authors: LA
authors: Deroo
authors: Dale P
authors: DP
authors: Sandler
authors: Clarice R
authors: CR
authors: Weinberg
mesh_terms: D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000139:chemically induced*; D016022:Case-Control Studies; D002996:Clomiphene / Q000008:administration & dosage / Q000009:adverse effects; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005299:Fertility Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011960:Receptors, Estrogen / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D035781:Siblings
chemical_list: D014408:Biomarkers, Tumor; D004965:Estrogen Antagonists; D005299:Fertility Agents; D011960:Receptors, Estrogen; D002996:Clomiphene; D005640:Follicle Stimulating Hormone