Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study
- Equal contributors
1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2 Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet and Hospital, Stockholm, Sweden
3 Bristol-Myers Squibb, Princeton, NJ, USA
4 Genome Institute of Singapore, Republic of Singapore
5 Department of Pathology, Uppsala University Hospital, Uppsala, Sweden
BMC Medicine 2006, 4:16 doi:10.1186/1741-7015-4-16Published: 30 June 2006
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.