Published in:
Open Access
01-12-2006 | Research article
Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study
Authors:
Per Hall, Alexander Ploner, Judith Bjöhle, Fei Huang, Chin-Yo Lin, Edison T Liu, Lance D Miller, Hans Nordgren, Yudi Pawitan, Peter Shaw, Lambert Skoog, Johanna Smeds, Sara Wedrén, John Öhd, Jonas Bergh
Published in:
BMC Medicine
|
Issue 1/2006
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Abstract
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 was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen.
Conclusion
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.