Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo

Background: High mammographic density is associated with increased breast c ancer risk, Previous studies have shown that estrogens increase breast dens ity on mammograms, but the effect on mammographic density of selective estr ogen receptor modulators, such as raloxifene, is unknown. We assessed chang es in mammographic density among women receiving placebo, raloxifene, or co njugated equine estrogens in an osteoporosis prevention trial. Methods: In a 5-year multicenter, double-blind, randomized, placebo-controlled osteopor osis prevention trial, healthy postmenopausal women who had undergone hyste rectomy less than 15 years before the study and had no history of breast ca ncer received placebo, raloxifene (at one of two doses), or conjugated estr ogens (ERT), Women from English-speaking investigative sites who had baseli ne and 2-year craniocaudal mammograms with comparable positioning (n = 168) were eligible for this analysis. Changes in mammographic density were dete rmined by digital scanning and computer-assisted segmentation of mammograms and were analyzed with the use of analysis of variance. All statistical te sts were two-sided. Results: Among the four treatment groups after 2 years on study, the mean breast density (craniocaudal view) was statistically sig nificantly greater in the ERT group than it was in the other three groups ( P<.01 for all three comparisons). Within treatment groups, the mean breast density from baseline to 2 years decreased statistically significantly in w omen receiving the placebo or either the higher or lower raloxifene dose (P =.003, P =.002, and P<.001, respectively) and showed a nonstatistically si gnificant increase in women receiving ERT, Conclusions: In an osteoporosis prevention trial, raloxifene did not increase breast density after 2 years of treatment. Raloxifene administration should not interfere with, and coul d even enhance, mammographic detection of new breast cancers.