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J Clin Oncol. 2009 Dec 20;27(36):6135-43. doi: 10.1200/JCO.2008.21.7166. Epub 2009 Nov 9.

Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the women's health initiative randomized trial.

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  • 1Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, M4-B874, PO Box 19024, Seattle, WA 98019, USA.



Increased mammographic density is associated with increased breast cancer risk and reduced sensitivity of screening mammography and is related to hormone exposure. However, the effects of conjugated equine estrogens (CEEs) alone on mammographic density in diverse racial/ethnic populations are not established. We examined the effect of CEE alone on mammographic density in a subsample of the Women's Health Initiative (WHI) clinical trial participants.


In the WHI trial, women were randomly assigned to daily CEE 0.625 mg or placebo. The effect of CEE on mammographic percent density was determined over 1 and 2 years in a stratified random sample of 435 racially and ethnically diverse participants from 15 of 40 WHI clinics.


Use of CEE resulted in mean increase in mammographic percent density of 1.6 percentage points (95% CI, 0.8 to 2.4) at year 1 compared with a mean decrease of 1.0 percentage point (95% CI, -1.7 to -0.4) in the placebo group (P < .001). The effect persisted for 2 years, with a mean increase of 1.7 percentage points (95% CI, 0.7 to 2.7) versus a mean decrease of 1.2 percentage points (95% CI, -1.8 to -0.5; P < .001) in the hormone and placebo groups, respectively. These effects were greater in women age 60 to 79 years (P = .03 for interaction across age).


Use of CEE results in a modest but statistically significant increase in mammographic density that is sustained over at least a 2-year period. The clinical significance of the CEE effect on mammographic density remains to be determined.

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