Estrogen and colorectal cancer incidence and mortality in the Women's Health Initiative clinical trial.

Abstract

3594 Background: The preponderance of observational studies associate estrogen alone use with lower colorectal cancer incidence. In contrast, no difference in colorectal cancer incidence was seen in the Women's Health Initiative (WHI) randomized, controlled trial (RCT) of estrogen versus placebo after 7.1 years mean intervention. We now assess the influence of estrogen alone use on longer-term colorectal cancer incidence and mortality after an additional 5.6 years post-intervention follow-up. Methods: The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 10,739 postmenopausal women who had undergone prior hysterectomy and who were randomly assigned to receive daily 0.625 conjugated equine estrogen (n = 5279) or matching placebo (n = 5409). Colorectal cancer diagnosis rates and mortality were assessed after a mean of 7.1 years (standard deviation [SD] 1.1) of intervention and 12.7 years follow-up. Results: Colorectal cancer incidence in the treatment and control groups were almost equivalent, 0.15% diagnoses/year v 0.13% in the estrogen therapy arm and the placebo group, respectively (Hazard ratio [HR], 1.12; 95% Confidence Interval [CI], 0.83-1.52; P = 0.46). Bowel screening examinations were comparable in both groups throughout. For women age 70-79 at study entry, hormone therapy was associated with an increased risk of colorectal cancer, HR 1.71; 95% CI, (1.02-2.86). For women age 50-59 and 60-69, the respective HR’s and 95% CI were 0.86 (0.43-1.71) and 0.98 (0.64-1.49), p-interaction 0.165. For women with a waist circumference of > 88 cm, there was an increased risk of colorectal cancer, HR 1.53; 95% CI, 0.95-2.45 compared to 0.95 (0.66-1.39) for waist circumference of < 88 cm, p-interaction 0.124. Although not statistically significant, there was a higher number of colorectal cancer deaths in the hormone therapy arm (33 v 24 deaths; 0.05% v 0.04%; HR, 1.42; 95% CI, 0.84-2.41; P = 0.19). Conclusions: There were no significant differences in colorectal cancer incidence or mortality after long-term follow-up in the WHI RCT of conjugated equine estrogen. There was a suggestion of an elevation in colorectal cancer risk among older women randomized to estrogen. Clinical trial information: NCT00000611.