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Research article
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Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study
Per Hall , Alexander Ploner , Judith Bjohle , Fei Huang , Chin-Yo Lin , Edison T Liu , Lance D Miller , Hans Nordgren , Yudi Pawitan , Peter Shaw , Lambert Skoog , Johanna Smeds , Sara Wedren , John Ohd and Jonas Bergh

BMC Medicine 2006, 4:16 doi:10.1186/1741-7015-4-16

Published 30 June 2006

Abstract (provisional)

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.


Background

Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.

Methods

We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women.

Results

HRT use in patients with estrogen receptor (ER) protein positive tumors (n=72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT use negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen.

Conclusions

Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.