Low Levels of Estrogen Receptor β Protein Predict Resistance to Tamoxifen Therapy in Breast Cancer
Open Access
- 15 November 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 10 (22) , 7490-7499
- https://doi.org/10.1158/1078-0432.ccr-04-1114
Abstract
Purpose: Breast cancer is a hormone-dependent cancer, and the presence of estrogen receptor α (ER-α) in tumors is used clinically to predict the likelihood of response to hormonal therapies. The clinical value of the second recently identified ER isoform, called ER-β, is less clear, and there is currently conflicting data concerning its potential role as a prognostic or predictive factor. Experimental Design: To assess whether ER-β expression is associated with clinical outcome, protein levels were measured by immunoblot analysis of a retrospective bank of tumor cell lysates from 305 axillary node-positive patients. A total of 119 received no adjuvant therapy, and 186 were treated with tamoxifen only. The median follow-up time was 65 months. Univariate and multivariate Cox regression modeling was done to assess the prognostic and predictive significance of ER-β expression. Results: Expression of ER-β protein did not correlate significantly with any other clinical variables, including ER and progesterone levels (as measured ligand binding assay), tumor size, age, or axillary nodal status. In the untreated population, those patients whose tumors who expressed both receptor isoforms exhibited the most favorable outcome as compared with those patients who had lost ER-α expression. However, there was no association between ER-β levels alone and either disease-free or overall survival in the untreated patient population. In contrast, in both univariate and multivariate analyses, high levels of ER-β predicted an improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy. Conclusions: These findings provide evidence that ER-β may be an independent predictor of response to tamoxifen in breast cancer. Furthermore, these results suggest that ER-β may influence tumor progression in ways different from those mediated by the ER-α isoform.Keywords
This publication has 45 references indexed in Scilit:
- Evaluation of oestrogen receptor β wild-type and variant protein expression, and relationship with clinicopathological factors in breast cancersEuropean Journal Of Cancer, 2002
- Involvement of estrogen receptor β in terminal differentiation of mammary gland epitheliumProceedings of the National Academy of Sciences, 2002
- Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trialThe Lancet, 2002
- Clinicopathological Characteristics of Estrogen Receptor‐(3‐positive Human Breast CancersJapanese Journal of Cancer Research, 2001
- Tissue Distribution and Quantitative Analysis of Estrogen Receptor- (ER ) and Estrogen Receptor- (ER ) Messenger Ribonucleic Acid in the Wild-Type and ER -Knockout MouseEndocrinology, 1997
- Differential Ligand Activation of Estrogen Receptors ERα and ERβ at AP1 SitesScience, 1997
- Estrogen Receptors α and β Form Heterodimers on DNAJournal of Biological Chemistry, 1997
- ERβ: Identification and characterization of a novel human estrogen receptorFEBS Letters, 1996
- Cloning of a novel receptor expressed in rat prostate and ovary.Proceedings of the National Academy of Sciences, 1996
- Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 womenThe Lancet, 1992