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16813654
Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.

BMC Med, 2006/6/30;4:16.

Hall P[1], Ploner A, Bjöhle J, Huang F, Lin CY, Liu ET, Miller LD, Nordgren H, Pawitan Y, Shaw P, Skoog L, Smeds J, Wedrén S, Ohd J, Bergh J

Affiliations

PMID: 16813654

Impact factor: 11.15

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.
MeSH terms
Breast Neoplasms; Cell Line, Tumor; Cohort Studies; DNA Primers; Disease-Free Survival; Estrogen Replacement Therapy; Female; Gene Expression Profiling; Humans; Postmenopause; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Survival Analysis; Transcription, Genetic
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