Postmenopausal Hormone Therapy and Change in Mammographic Density

Background: Mammographic density is an independent risk factor for breast cancer. Postmenopausal hormone use is associated with an increase in mammographic density, but the magnitude of the density increase is unknown. Methods: Baseline and 12-month mammograms were obtained for 571 (65%) of the 875 women, aged 45–64 years, who were enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial and randomly assigned to receive placebo, daily conjugated equine estrogens at 0.625 mg/day (CEE), daily CEE and medroxyprogesterone acetate (MPA) at 10 mg/day on days 1–12 (CEE+MPA-cyclic), daily CEE and MPA at 2.5 mg/day (CEE+MPA-continuous), or daily CEE and micronized progesterone (MP) at 200 mg/day on days 1–12 (CEE+MP). We analyzed digitized mammograms to determine the percentage of the left breast that was composed of dense tissue (i.e., mammographic percent density). Linear regression analysis was used to examine the effects of treatments on the change in mammographic percent density between baseline and 12 months, before and after adjustment for possible confounders. All statistical tests were two-sided. Results: The adjusted absolute mean changes in mammographic percent density over 12 months were 4.76% (95% confidence interval [CI] = 3.29% to 6.23%), 4.58% (95% CI = 3.19% to 5.97%), and 3.08% (95% CI = 1.65% to 4.51%) for women in the CEE+MPA-cyclic, CEE+MPA-continuous, and CEE-MP groups, respectively. Each of those absolute mean changes was statistically significantly different from the adjusted absolute mean change in mammographic percent density for women in the placebo group, which was –0.07% (95% CI = –1.50% to 1.38%). Conclusion: Greater mammographic density was associated with the use of estrogen/progestin combination therapy, regardless of how the progestin was given, but not with the use of estrogen only. [J Natl Cancer Inst 2003;95:30–7]