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Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer.
Clin Cancer Res. 2004 Nov 15; 10(22):7490-9.CC

Abstract

PURPOSE

Breast cancer is a hormone-dependent cancer, and the presence of estrogen receptor alpha (ER-alpha) 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-beta, 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-beta 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-beta expression.

RESULTS

Expression of ER-beta 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-alpha expression. However, there was no association between ER-beta 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-beta predicted an improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy.

CONCLUSIONS

These findings provide evidence that ER-beta may be an independent predictor of response to tamoxifen in breast cancer. Furthermore, these results suggest that ER-beta may influence tumor progression in ways different from those mediated by the ER-alpha isoform.

Authors+Show Affiliations

Department of Medicine, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15569979

Citation

Hopp, Torsten A., et al. "Low Levels of Estrogen Receptor Beta Protein Predict Resistance to Tamoxifen Therapy in Breast Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 10, no. 22, 2004, pp. 7490-9.
Hopp TA, Weiss HL, Parra IS, et al. Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. Clin Cancer Res. 2004;10(22):7490-9.
Hopp, T. A., Weiss, H. L., Parra, I. S., Cui, Y., Osborne, C. K., & Fuqua, S. A. (2004). Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 10(22), 7490-9.
Hopp TA, et al. Low Levels of Estrogen Receptor Beta Protein Predict Resistance to Tamoxifen Therapy in Breast Cancer. Clin Cancer Res. 2004 Nov 15;10(22):7490-9. PubMed PMID: 15569979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. AU - Hopp,Torsten A, AU - Weiss,Heidi L, AU - Parra,Irma S, AU - Cui,Yukun, AU - Osborne,C Kent, AU - Fuqua,Suzanne A W, PY - 2004/12/1/pubmed PY - 2005/5/18/medline PY - 2004/12/1/entrez SP - 7490 EP - 9 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 10 IS - 22 N2 - PURPOSE: Breast cancer is a hormone-dependent cancer, and the presence of estrogen receptor alpha (ER-alpha) 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-beta, 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-beta 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-beta expression. RESULTS: Expression of ER-beta 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-alpha expression. However, there was no association between ER-beta 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-beta predicted an improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy. CONCLUSIONS: These findings provide evidence that ER-beta may be an independent predictor of response to tamoxifen in breast cancer. Furthermore, these results suggest that ER-beta may influence tumor progression in ways different from those mediated by the ER-alpha isoform. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15569979/Low_levels_of_estrogen_receptor_beta_protein_predict_resistance_to_tamoxifen_therapy_in_breast_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15569979 DB - PRIME DP - Unbound Medicine ER -