Low-dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

Objective: The aim of this study was to investigate whether transdermal low-dose estradiol treatment induces changes in mammographic density or heterogeneity compared with raloxifene, whether if these changes relate to changes in bone formation/resorption markers, and whether these findings indicate elevation of breast cancer risk by treatment. Methods: Digitized mammograms of 2 x 135 completers of a 2-year, randomized trial formed the base of the present analysis. Active treatments were transdermal estradiol releasing 0.014 mg estradiol (E(2))/week and orally administered raloxifene hydrochloride 60 mg/day, respectively. Influence of the therapies on breast density was assessed with categorical scores Breast Imaging Reporting and Data System, area percentage density, and computer-based (E(2)-specific) heterogeneity examination of radiographs. These where related to physical and systemic markers. Results: At baseline, no mammography scoring methodology or other marker could separate the two treatment groups of transdermal estradiol and raloxifene. No treatment induced significant density changes measured by Breast Imaging Reporting and Data System. Both treatments made the area percentage density increase and the estradiol significantly. Both treatments induced significant changes in E(2)-specific heterogeneity scoring (E(2)-specific heterogeneity examination of radiograph), and the raloxifene treatment induced a significantly higher change. At baseline, the mammographic markers showed negative correlation with body mass index and positive correlation with serum type I collagen crosslinks C-telopeptide. The changes in mammographic markers did not essentially exhibit correlations to changes in bone markers in either treatment group. Conclusions: Low-dose transdermal estradiol and raloxifene induced comparable changes in breast density and heterogeneity. Baseline correlations may be explained through relations to obesity. The current study does not yield evidence against the hypothesis that neither raloxifene nor low dose transdermal estradiol treatment increases the breast cancer risk.