Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer.
OBJECTIVE
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.


METHODS
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.
Hopp
Torsten A
TA
Department of Medicine, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.
Weiss
Heidi L
HL
Parra
Irma S
IS
Cui
Yukun
Y
Osborne
C Kent
CK
Fuqua
Suzanne A W
SA
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000502:physiology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; D047629:Estrogen Receptor beta; D008024:Ligands; D020033:Protein Isoforms; D013629:Tamoxifen