Originally published as JCO Early Release 10.1200/JCO.2005.04.7332 on February 20 2007

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Postmenopausal Hormone Therapy and Changes in Mammographic Density

Fränzel J.B. van Duijnhoven, Petra H.M. Peeters, Ruth M.L. Warren, Sheila A. Bingham, Paulus A.H. van Noord, Evelyn M. Monninkhof, Diederick E. Grobbee, Carla H. van Gils

From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Radiology, Addenbrooke's Hospital, Cambridge Breast Unit; and Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom

Address reprint requests to Carla H. van Gils, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Mail-drop Str 6.131, PO Box 85500, 3508 GA Utrecht, the Netherlands; e-mail: C.vangils{at}umcutrecht.nl

Purpose Hormone therapy (HT) use has been associated with an increased breast cancer risk. We explored the underlying mechanism further by determining the effects of HT on mammographic density, a measure of dense tissue in the breast and a consistent breast cancer risk factor.

Patients and Methods A total of 620 HT users and 620 never users from the Dutch Prospect–European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 175 HT users and 161 never users from the United Kingdom EPIC–Norfolk cohort were included. For HT users, one mammogram before and one mammogram during HT use was included. For never users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression.

Results The median time between mammograms was 3.0 years and the median duration of HT use was 1 year. The absolute mean decline in percent density was larger in never users (7.3%) than in estrogen therapy users (6.4%; P = .22) and combined HT users (3.5%; P < .01). The effect of HT appeared to be high in a small number of women, whereas most women were unaffected.

Conclusion Our results suggest that HT use, and especially estrogen and progestin use, slows the changes from dense patterns to more fatty patterns that are normally seen in women with increasing age. Given that it is postulated that lifetime cumulative exposure to high density may be related to breast cancer risk, a delay in density decline in HT users potentially could explain their increased breast cancer risk.

published online ahead of print at www.jco.org on February 20, 2007.

Supported by the Dutch Cancer Society Grant No. UU 2002-2716.

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

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