Estrogen Receptor β Expression Is Associated with Tamoxifen Response in ERα-Negative Breast Carcinoma
| Autor: | Mårten Fernö, Cecilia Hegardt, Pär-Ola Bendahl, Lao H. Saal, Åke Borg, Jorma Isola, Mervi Laakso, Carsten Peterson, Per-Uno Malmström, Sofia K. Gruvberger-Saal, Patrik Edén |
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| Rok vydání: | 2007 |
| Předmět: |
Selective Estrogen Receptor Modulators
Oncology Cancer Research medicine.medical_specialty Gene Expression Estrogen receptor Breast Neoplasms Kaplan-Meier Estimate Breast cancer Internal medicine Biomarkers Tumor medicine Estrogen Receptor beta Humans Estrogen receptor beta Oligonucleotide Array Sequence Analysis Randomized Controlled Trials as Topic business.industry Gene Expression Profiling Estrogen Receptor alpha Cancer Prognosis Antiestrogen medicine.disease Immunohistochemistry Tamoxifen Endocrinology Chemotherapy Adjuvant Selective estrogen receptor modulator Female business Estrogen receptor alpha medicine.drug |
| Zdroj: | Clinical Cancer Research. 13:1987-1994 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-06-1823 |
| Popis: | Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERα)–positive breast carcinoma but are not indicated for persons with ERα-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERα-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERβ, in patients treated with adjuvant tamoxifen. Experimental Design: We investigated ERβ by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors. Results: ERβ was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERα-negative patients (P = 0.003; P = 0.04), but not in the ERα-positive subgroup (P = 0.49; P = 0.88). Lack of ERβ conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERα-negative subgroup even after adjustment for other markers. ERα was an independent marker only within the ERβ-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERβ gene expression profile was identified and was markedly different from the ERα signature. Conclusion: Expression of ERβ is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERα-negative breast cancer patients and involves a gene expression program distinct from ERα. These results may be highly clinically significant, because in the United States alone, ∼10,000 women are diagnosed annually with ERα-negative/ERβ-positive breast carcinoma and may benefit from adjuvant tamoxifen. |
| Databáze: | OpenAIRE |
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