Estrogen receptor β expression is associated with tamoxifen response in ERα-negative breast carcinoma
Estrogen receptor β expression is associated with tamoxifen response in ERα-negative breast carcinoma
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DOI：
10.1158/1078-0432.ccr-06-1823
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发表时间：
2007-04-01
影响因子：
11.5
通讯作者：
Fernoe, Marten
中科院分区：
文献类型：
--
作者：
Gruvberger-Saal, Sofia K.;Bendahl, Paer-Ola;Fernoe, Marten
目的：内分泌治疗，如他莫昔芬，通常用于大多数雌激素受体(ERα)阳性乳腺癌患者，但不适用于ERα阴性乳腺癌患者。在ERα阴性的肿瘤患者中，5%到10%的患者对他莫昔芬有反应的因素尚不清楚。实验设计：我们用免疫组织化学方法研究了353例接受2年三苯氧胺辅助治疗的II期乳腺癌患者的ERβ，并生成了88个肿瘤的代表性亚群的基因表达谱。结果：ERβ与生存率(远距离无病生存，P=0.01；总生存率，P=0.22)相关，尤其是在ERα阴性的患者中(P=0.003；P=0.04)，而在ERα阳性亚组中无明显差异(P=0.49；P=0.88)。在ERα阴性亚组中，即使在调整了其他标记物后，缺乏ERβ也会导致早期复发(风险比为14；95%可信区间为1.8-106；P=0.01)。ERα仅在ERβ阴性的肿瘤中是一个独立的标记物(风险比0.44；95%可信区间0.21-0.89；P=0.02)。结论：ERβ的表达是ERα阴性乳腺癌患者接受三苯氧胺辅助治疗后预后良好的独立标志，并涉及不同于ERα的基因表达程序。这些结果可能具有高度的临床意义，因为仅在美国，每年就有大约10,000名妇女被诊断为ERα阴性/ERβ阳性乳腺癌，并可能受益于辅助剂他莫昔芬。
Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ER alpha) -positive breast carcinoma but are not indicated for persons with ER alpha-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ER alpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ER beta, in patients treated with adjuvant tamoxifen.Experimental Design: We investigated ER beta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.Results: ER beta was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ER alpha-negative patients (P = 0.003; P = 0.04), but not in the ER alpha-positive subgroup (P = 0.49; P = 0.88). Lack of ER beta conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ER alpha-negative subgroup even after adjustment for other markers. ER alpha was an independent marker only within the ER beta-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ER beta gene expression profile was identified and was markedly different from the ER alpha signature.Conclusion: Expression of ER beta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ER alpha-negative breast cancer patients and involves a gene expression program distinct from ER alpha. These results may be highly clinically significant, because in the United States alone, similar to 10,000 women are diagnosed annually with ER alpha-negative/ER beta-positive breast carcinoma and may benefit from adjuvant tamoxifen.