Clinical importance of estrogen receptor-β evaluation in breast cancer patients treated with adjuvant tamoxifen therapy

Document Type

Journal Article

Publication Date

9-22-2008

Journal

Journal of Clinical Oncology

Volume

26

Issue

22

DOI

10.1200/JCO.2007.14.2968

Abstract

Purpose: The clinicopathologic importance of a second estrogen receptor (ER), ER-β, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-β assay, probably because of the lack of standardized methodology, the presence of several ER-β isotypes (ER-β1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-β status provides clinically useful information over what is already provided by the traditional ER-α/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues. Patients and Methods: Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and with a long follow-up period (median, 11.1 years) were subjected to immunohistochemical study using three commercially available anti-ER-β antibodies that detect ER-β1-3 (ER-βN), ER-β1, and ER-βcx (ER-β2). Results: Positive staining for ER-βN or ER-β1 was associated with significantly better survival. By contrast, ER-βcx status did not influence survival. In multivariate analysis, ER-β1 status emerged as an independent predictor of recurrence and mortality. ER-β1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-β1 positivity was associated with significantly better survival in patients with ER-α-negative/PR-negative or ER-α-negative/PR-negative/human epidermal growth factor receptor 2-negative (triple-negative) tumors, which are widely believed to be hormone unresponsive, have poor prognosis, and require chemotherapy. Conclusion: Immunohistochemical examination of ER-β1 in addition to ER-α and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings. © 2008 by American Society of Clinical Oncology.

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