title: Unopposed estrogen therapy and the risk of invasive breast cancer.
abstract: BACKGROUND
  Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period.
  
  
  METHODS
  Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline (1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer.
  
  
  RESULTS
  A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor (ER+) and progesterone receptor (PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 (95% CI, 0.75-1.22), 0.90 (95% CI, 0.73-1.12), 1.06 (95% CI, 0.87-1.30), 1.18 (95% CI, 0.95-1.48), and 1.42 (95% CI, 1.13-1.77) (P for trend <.001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07).
  
  
  CONCLUSIONS
  Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.
authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. wendy.chen@channing.harvard.edu
authors: Wendy Y
authors: WY
authors: Chen
authors: JoAnn E
authors: JE
authors: Manson
authors: Susan E
authors: SE
authors: Hankinson
authors: Bernard
authors: B
authors: Rosner
authors: Michelle D
authors: MD
authors: Holmes
authors: Walter C
authors: WC
authors: Willett
authors: Graham A
authors: GA
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