Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study
2006 (English)In: BMC Medicine, ISSN 1741-7015, Vol. 4, 16- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2006. Vol. 4, 16- p.
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
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-11035DOI: 10.1186/1741-7015-4-16ISI: 000244870400001PubMedID: 16813654OAI: oai:DiVA.org:uu-11035DiVA: diva2:38803