Low levels of estrogen receptor β protein predict resistance to tamoxifen therapy in breast cancer
Low levels of estrogen receptor β protein predict resistance to tamoxifen therapy in breast cancer
复制标题
DOI：
10.1158/1078-0432.ccr-04-1114
复制
发表时间：
2004-11-15
影响因子：
11.5
通讯作者：
Fuqua, SAW
中科院分区：
文献类型：
--
作者：
Hopp, TA;Weiss, HL;Fuqua, SAW
目的：乳腺癌是一种激素依赖性的癌症，肿瘤中雌激素受体α (er - α)的存在在临床上被用来预测激素治疗应答的可能性。最近发现的第二种内质网异构体（ER- β）的临床价值尚不清楚，目前关于其作为预后或预测因素的潜在作用的数据存在矛盾。实验设计：为了评估ER-P表达是否与临床结果相关，通过免疫印迹分析305例腋窝淋巴结阳性患者的回顾性肿瘤细胞分离物来测量蛋白水平。119例患者未接受辅助治疗，186例仅接受他莫昔芬治疗。中位随访时间为65个月。采用单因素和多因素Cox回归模型评估er - β表达的预后和预测意义。结果：ER- β蛋白的表达与任何其他临床变量，包括ER和黄体酮水平（测量配体结合试验）、肿瘤大小、年龄或腋窝淋巴结状态均无显著相关性。在未经治疗的人群中，与失去er - α表达的患者相比，表达两种受体亚型的肿瘤患者表现出最有利的结果。然而，在未经治疗的患者群体中，er - β水平单独与无病或总生存率之间没有关联。相比之下，在单变量和多变量分析中，高水平的er - β预示着接受辅助他莫昔芬治疗的患者无病生存期和总生存期的改善。结论：这些发现提供了er - β可能是乳腺癌对他莫昔芬反应的独立预测因子的证据。此外，这些结果表明，er - β可能以不同于er - α亚型介导的方式影响肿瘤进展。
Purpose: 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.Experimental Design: To assess whether ER-P 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.