Fertility drugs and young-onset breast cancer: results from the Two Sister Study

J Natl Cancer Inst. 2012 Jul 3;104(13):1021-7. doi: 10.1093/jnci/djs255. Epub 2012 Jul 6.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / chemically induced*
  • Case-Control Studies
  • Clomiphene / administration & dosage
  • Clomiphene / adverse effects
  • Estrogen Antagonists / administration & dosage
  • Estrogen Antagonists / adverse effects
  • Female
  • Fertility Agents / administration & dosage*
  • Fertility Agents / adverse effects*
  • Follicle Stimulating Hormone / administration & dosage
  • Follicle Stimulating Hormone / adverse effects
  • Humans
  • Logistic Models
  • Odds Ratio
  • Pregnancy Trimester, First
  • Pregnancy Trimester, Second
  • Pregnancy*
  • Receptors, Estrogen / analysis
  • Risk Assessment
  • Risk Factors
  • Siblings


  • Biomarkers, Tumor
  • Estrogen Antagonists
  • Fertility Agents
  • Receptors, Estrogen
  • Clomiphene
  • Follicle Stimulating Hormone