Combination hormone therapy associated with increase in breast density

December 31, 2002

A new study suggests that the use of combination hormone therapy, but not estrogen alone, is associated with a modest increase in breast density, a known risk factor for breast cancer. The findings appear in the January 1 issue of the Journal of the National Cancer Institute.

The degree of breast cancer risk that is associated with breast density is greater than that associated with almost all other known breast cancer risk factors. A previous analysis of data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized trial looking at the effects of postmenopausal hormone therapy (estrogen alone or estrogen plus three different progestin regimens) on breast density, showed that some women who used combination estrogen/progestin therapy experienced an increase in breast density. However, the analysis did not look at the magnitude of that increase. Past studies have suggested that the greater the breast density, the greater the risk for breast cancer.

Gail A. Greendale, M.D., of the University of California Los Angeles School of Medicine, and her colleagues examined digitized mammograms at baseline and after one year of therapy from 571 postmenopausal women enrolled in the PEPI trial who were randomly assigned to receive daily doses of estrogen alone, estrogen plus cyclic medroxyprogesterone acetate, estrogen plus continuous medroxyprogesterone acetate, estrogen plus micronized progesterone, or a placebo.

They found that use of estrogen/progestin combination therapy, regardless of how the progestin was given, was associated with 3% to 5% increases in breast density. Use of estrogen alone was not associated with such increases in breast density.

The authors conclude that the use of combination hormone therapy, but not the use of estrogen alone, is associated with increases in breast density. "However, the link between change in breast density resulting from hormone use and change in breast cancer risk remains uncertain," they say.

In an accompanying editorial, Rowan T. Chlebowski, M.D., Ph.D., of the Harbor-UCLA Research and Education Institute in Torrance, Calif., and Anne McTiernan, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, point out that breast density is a useful marker of increased risk for breast cancer, and they add that breast density may be a valid marker of the effect of interventions that increase or decrease breast cancer risk.
Contact: Kirsten Holguin, UCLA, 310-794-0777; fax: 310-794-2259,

Editorial: Pamela Clem, Harbor-UCLA Research and Education Institute, 310-222-7922; fax: 310-782-0486,

Greendale G, Reboussin B, Slone S, Wasilauskas C, Pike M, Ursin G. Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 2003;95:30-7.

Editorial: Chlebowski R, McTiernan A. Biological significance of interventions that change breast density. J Natl Cancer Inst 2003;95:4-5.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.

Journal of the National Cancer Institute

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