Clinical Importance of Estrogen Receptor-β Evaluation in Breast Cancer Patients Treated With Adjuvant Tamoxifen Therapy

PURPOSE: The clinicopathologic importance of a second estrogen receptor (ER), ER-beta, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-beta assay, probably because of the lack of standardized methodology, the presence of several ER-beta isotypes (ER-beta1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-beta status provides clinically useful information over what is already provided by the traditional ER-alpha/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-beta antibodies that detect ER-beta1-3 (ER-betaN), ER-beta1, and ER-betacx (ER-beta2). RESULTS: Positive staining for ER-betaN or ER-beta1 was associated with significantly better survival. By contrast, ER-betacx status did not influence survival. In multivariate analysis, ER-beta1 status emerged as an independent predictor of recurrence and mortality. ER-beta1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-beta1 positivity was associated with significantly better survival in patients with ER-alpha-negative/PR-negative or ER-alpha-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-beta1 in addition to ER-alpha and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings.