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Post-Treatment Change in Serum Estrone Predicts Mammographic Percent Density Changes in Women Who Received Combination Estrogen and Progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial

From the Department of Preventive Medicine/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine; David Geffen School of Medicine at University of California, Division of Geriatric Medicine, Los Angeles, CA; Department of Nutrition, University of Oslo, Norway; and Wake Forest University School of Medicine, Department of Public Health Sciences, Winston-Salem, NC

Address correspondence to Giske Ursin, MD, PhD, Department of Preventive Medicine, Norris Comprehensive Cancer Center, Room 4407, USC Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA 90089; e-mail: gursin{at}usc.edu

PURPOSE: Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density.

METHODS: We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year.

RESULTS: Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P = .0003). The absolute increases were 4.09% (P = .0018) in the CEE + MPA continuous group, 2.79% (P = .0292) in the CEE + MPA cyclical group, and 1.40% (P = .36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant.

CONCLUSION: Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.

Supported by grant funding from the National Cancer Institute, R-01 CA 77708, and by P30CA14089 (M.C.P.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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