Abstract
BackgroundPostmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.MethodsWe 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.ResultsHRT 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.ConclusionOur 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.
Highlights
ObjectivesWe aimed to compare gene expression of breast cancers in hormone-replacement therapy (HRT) users and non-users and to correlate the expression pattern to recurrence-free survival
Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk
A preliminary study of the distribution of t statistics comparing gene expression between HRT users and non-users for all 88 patients indicated that the observed differences are almost exclusively due to the differences observed in the estrogen receptor (ER)-positive tumors, whereas the ER-negative tumors contribute little or no information on differential expres
Summary
We aimed to compare gene expression of breast cancers in HRT users and non-users and to correlate the expression pattern to recurrence-free survival. This liberal cut-off point was chosen because the aim of the present study was not to identify specific genes, but rather patterns of expression
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