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

• Published in: BMC medicine 2006-06, Vol.4 (1), p.16-16, Article 16
• Main Authors: Hall, Per, Ploner, Alexander, Bjöhle, Judith, Huang, Fei, Lin, Chin-Yo, Liu, Edison T, Miller, Lance D, Nordgren, Hans, Pawitan, Yudi, Shaw, Peter, Skoog, Lambert, Smeds, Johanna, Wedrén, Sara, Ohd, John, Bergh, Jonas
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - classification; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms/classification/diagnosis/genetics/mortality/pathology; Cell Line, Tumor; Cohort Studies; Disease-Free Survival; DNA Primers; Estrogen Replacement Therapy; Female; Gene Expression Profiling; Humans; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Postmenopause; Premenopause; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Survival Analysis; Transcription, Genetic
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/1741-7015-4-16

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.