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

• 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.

Nyckelord

Breast Neoplasms/classification/diagnosis/*genetics/mortality/pathology

Cell Line; Tumor

Cohort Studies

DNA Primers

Disease-Free Survival

Estrogen Replacement Therapy

Female

Gene Expression Profiling

Humans

Postmenopause

Premenopause

Receptors; Estrogen/*analysis

Receptors; Progesterone/*analysis

Survival Analysis

Transcription; Genetic

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)