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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer

Authors: Jordan M Reese, Vera J Suman, Malayannan Subramaniam, Xianglin Wu, Vivian Negron, Anne Gingery, Kevin S Pitel, Sejal S Shah, Heather E Cunliffe, Ann E McCullough, Barbara A Pockaj, Fergus J Couch, Janet E Olson, Carol Reynolds, Wilma L Lingle, Thomas C Spelsberg, Matthew P Goetz, James N Ingle, John R Hawse

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

The role and clinical value of ERβ1 expression is controversial and recent data demonstrates that many ERβ antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize ERβ1 expression across all sub-types of breast cancer using a validated antibody and determine the roles of this receptor in mediating response to multiple forms of endocrine therapy both in the presence and absence of ERα expression.

Methods

Nuclear and cytoplasmic expression patterns of ERβ1 were analyzed in three patient cohorts, including a retrospective analysis of a prospective adjuvant tamoxifen study and a triple negative breast cancer cohort. To investigate the utility of therapeutically targeting ERβ1, we generated multiple ERβ1 expressing cell model systems and determined their proliferative responses following anti-estrogenic or ERβ-specific agonist exposure.

Results

Nuclear ERβ1 was shown to be expressed across all major sub-types of breast cancer, including 25% of triple negative breast cancers and 33% of ER-positive tumors, and was associated with significantly improved outcomes in ERα-positive tamoxifen-treated patients. In agreement with these observations, ERβ1 expression sensitized ERα-positive breast cancer cells to the anti-cancer effects of selective estrogen receptor modulators (SERMs). However, in the absence of ERα expression, ERβ-specific agonists potently inhibited cell proliferation rates while anti-estrogenic therapies were ineffective.

Conclusions

Using a validated antibody, we have confirmed that nuclear ERβ1 expression is commonly present in breast cancer and is prognostic in tamoxifen-treated patients. Using multiple breast cancer cell lines, ERβ appears to be a novel therapeutic target. However, the efficacy of SERMs and ERβ-specific agonists differ as a function of ERα expression.
Appendix
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Metadata
Title
ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer
Authors
Jordan M Reese
Vera J Suman
Malayannan Subramaniam
Xianglin Wu
Vivian Negron
Anne Gingery
Kevin S Pitel
Sejal S Shah
Heather E Cunliffe
Ann E McCullough
Barbara A Pockaj
Fergus J Couch
Janet E Olson
Carol Reynolds
Wilma L Lingle
Thomas C Spelsberg
Matthew P Goetz
James N Ingle
John R Hawse
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-749

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