Original Contribution Conjugated Equine Estrogens and Breast Cancer Risk in the Women’s Health Initiative Clinical Trial and Observational Study

The Women’s Health Initiative randomized controlled trial found a trend (p 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone prepa-rations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women’s Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEEhazard ratio estimateswere higher from the observational study compared with the clinical trial by 43 % (p 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p 0.82). For wome