Clinicopathological importance of estrogen receptor-β in breast cancer of Japanese women

目的。第二种雌激素受体ER-β在乳腺癌中的临床病理重要性已被深入研究；然而，对于ER-β检测的临床应用，仍然没有真正的共识，可能是因为缺乏标准化的方法，存在几种ER-β同型（ER-β1-5等），更重要的是，缺乏令人信服的数据，关于ER-β状态是否比传统的雌激素受体(ER-α)/孕酮受体（PR）检测提供临床有用的信息。需要进行大规模和系统的研究来解决这些重要问题。材料和方法。采用四种市售抗er -β抗体对442例接受辅助单药他莫昔芬治疗的浸润性乳腺癌患者的档案资料进行了免疫组织化学研究，随访时间长（中位11.1年）；抗ER-β1单克隆、抗ER-βcx （= ER-β2）单克隆、抗ER-β1-3单克隆和抗ER-β1-3多克隆。尽管抗ER-β1单克隆抗体似乎是最好的标记物，但无论抗体是什么，ER-β表达与良好的预后相关。在多变量分析中，ER-β1状态成为一个独立的预后因素。ER-β1状态是绝经后妇女生存的重要预测因子，而不是绝经前妇女。ER-β1的预后价值在ER-α-阴性/ pr -阴性或ER-α-阴性/ pr -阴性/ her2阴性肿瘤患者中尤为明显，这类患者普遍认为激素反应不良，预后较差，需要化疗。除ER-α和PR外，免疫组化检查ER-β1对预测他莫昔芬单药治疗乳腺癌患者的生存具有重要的临床意义。ER-β1检测可优化乳腺癌治疗。

PURPOSE. The clinicopathological importance of a second estrogen receptor, 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, etc.) and, more importantly, the lack of convincing data on whether an ER-β status provides clinically useful information over what is already provided by the traditional estrogen receptor (ER-α)/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues.MATERIALS AND METHODS. Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and a long follow-up period (median 11.1 years) were subjected to immunohistochemical study using four commercially available anti-ER-β antibodies; anti-ER-β1 monoclonal, anti-ER-βcx (= ER-β2) monoclonal, anti-ER-β1-3 monoclonal, and anti-ER-β1-3 polyclonal.RESULTS. ER-β expression correlated with a favorable prognosis regardless of the antibody, although anti-ER-β1 monoclonal antibody appeared to be the best marker. In multivariate analysis, ER-β1 status emerged as an independent prognostic factor. ER-β1 status was a significant predictor of survival in postmenopausal, but not premenopausal, women. Prognostic value of ER-β1 is especially distinct among patients with ER-α-negative/PR-negative or ER-α-negative/PR-negative/HER2-negative tumors, a group of patients widely believed to be hormone unresponsive, have poor prognosis, and needing chemotherapy.CONCLUSION. Immunohistochemical examination of ER-β1 in addition to ER-α and PR is clinically important to predict survival of patients with breast cancer treated with tamoxifen monotherapy. ER-β1 examination may optimize breast cancer treatment.