Effect of ultra-low-dose transdermal estradiol on breast density in postmenopausal women

Objective: Women with higher mammographic breast density have increased risk for breast cancer, and there is some evidence that a change in breast density may be a marker for change in risk for breast cancer. The purpose of this study was to determine whether 2 years of treatment with ultra-low-dose transdermal estradiol results in a change in breast density. Design: The Ultra-Low-dose Transdermal Estradiol Assessment was a randomized, blinded, placebo-controlled trial of 2 years of treatment with unopposed ultra-low-dose (0.014 mg/d) transdermal estradiol for prevention of osteoporosis in 417 postmenopausal women with no history of breast cancer who had not had a hysterectomy. We obtained mammograms at baseline and after 1 and 2 years of treatment from 276 of the participants. Right craniocaudal views were analyzed at a central radiology facility by a trained clinician blinded to treatment group and order of acquisition. Contour analysis was performed to define dense areas versus fatty tissue. Between-group differences in mean change in percent breast density from baseline to 1 and to 2 years of follow-up were assessed using linear regression models adjusted for clinical site. Results: Participants were 66 ± 5 years old and 94% were white. The average percent breast density at baseline was 34%. There was no significant difference between treatment groups in change in percent breast density after 1 year (between-group difference, 0.1%; 95% confidence interval, -1.3% to 1.6%) or 2 years of treatment (0.8%; -0.6% to 2.1%). Conclusions: Two years of treatment with ultra-low-dose transdermal estradiol did not increase breast density.