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Open Access Highly Accessed Research article

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

Per Hall1, Alexander Ploner1*, Judith Bjöhle2, Fei Huang3, Chin-Yo Lin4, Edison T Liu4, Lance D Miller4, Hans Nordgren5, Yudi Pawitan1, Peter Shaw3, Lambert Skoog2, Johanna Smeds2, Sara Wedrén1, John Öhd2 and Jonas Bergh2

Author Affiliations

1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

2 Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet and Hospital, Stockholm, Sweden

3 Bristol-Myers Squibb, Princeton, NJ, USA

4 Genome Institute of Singapore, Republic of Singapore

5 Department of Pathology, Uppsala University Hospital, Uppsala, Sweden

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

Published: 30 June 2006



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.


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.


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 was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen.


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.