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

被引:39
作者
Hall, Per
Ploner, Alexander [1 ]
Bjohle, Judith
Huang, Fei
Lin, Chin-Yo
Liu, Edison T.
Miller, Lance D.
Nordgren, Hans
Pawitan, Yudi
Shaw, Peter
Skoog, Lambert
Smeds, Johanna
Wedren, Sara
Ohd, John
Bergh, Jonas
机构
[1] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden
[2] Karolinska Inst & Hosp, Canc Ctr Karolinska, Dept Oncol & Pathol, S-10401 Stockholm, Sweden
[3] Bristol Myers Squibb Co, Princeton, NJ 08543 USA
[4] Genome Inst Singapore, Singapore, Singapore
[5] Univ Uppsala Hosp, Dept Pathol, S-75014 Uppsala, Sweden
关键词
D O I
10.1186/1741-7015-4-16
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:13
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