Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy
Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy
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DOI：
10.1158/1078-0432.ccr-06-1842
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发表时间：
2007-01-15
影响因子：
11.5
通讯作者：
Poremba, Christopher
中科院分区：
文献类型：
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作者：
Diallo-Danebrock, Raihanatou;Ting, Evelyn;Poremba, Christopher
目的：为了表征蛋白质表达谱在高危乳腺癌患者中的预后和预测性影响，这些患者先前已被证明与剂量密集化疗（DDCT）相比，从高剂量化疗（HDCT）中获益。使用含有石蜡包埋的组织微阵列评估34种蛋白质标记物的表达。来自236名随机分配到西德研究组AM 01试验的患者的嵌入式乳腺癌样本。（a）34个标志物的初始组中的24个蛋白质标志物足以鉴定5个谱簇通过K-均值聚类分析，可以确定不同类型（亚型）的基因型：管腔-A（27%）、管腔-B（12%）、HER-2（21%）、基底样（13%）簇和所谓的“多标记阴性”（MMN）簇（27%），其特征在于不存在指定标记。(b)DDCT后，HER-2组和基底细胞样组的无事件生存率显著低于两个管腔型组[EFS;风险比（HR），分别为3.6 [95%置信区间（95% CI），1.65-8.18; P = 0.0011和HR，3.7（95% CI，1.68-8.48; P < 0.0001）]。(c)HDCT后HR为1.5 HER-2亚组中EFS的95% CI，0.76-3.05，1.1（95% CI，0.37-3.32），这表明接受HDCT的HER-2和基底细胞样亚组患者的结局更好。与DDCT相比，MMN簇显示HDCT后EFS更好的趋势。结论：高危乳腺癌的蛋白质表达谱确定了五种亚型，其在生存和对化疗的反应方面不同：与管腔A和管腔B亚型相比，HER-2和基底样亚组具有显著的预测益处，MMN簇具有预测益处的趋势，两者都来自HDCT与DDCT相比。
Purpose: To characterize the prognostic and predictive impact of protein expression profiles in high-risk breast cancer patients who had previously been shown to benefit from high-dose chemotherapy (HDCT) in comparison to dose-dense chemotherapy (DDCT).Experimental Design: The expression of 34 protein markers was evaluated using tissue microarrays containing paraffin-embedded breast cancer samples from 236 patients who were randomized to the West German Study Group AM01 trial.Results: (a) 24 protein markers of the initial panel of 34 markers were sufficient to identify five profile clusters (subtypes) by K-means clustering: luminal-A (27%), luminal-B (12%), HER-2 (21%), basal-like (13%) cluster, and a so-called "multiple marker negative" (MMN) cluster (27%) characterized by the absence of specifying markers. (b) After DDCT HER-2 and basal-like groups had significantly worse event-free survival [EFS; hazard ratio (HR), 3.6 [95% confidence interval (95% CI), 1.65-8.18; P = 0.0011 and HR, 3.7 (95% Cl, 1.68-8.48; P < 0.0001), respectively] when compared with both luminal groups. (c) After HDCT the HR was 1.5 (95% Cl, 0.76-3.05) for EFS in the HER-2 subgroup and 1.1 (95% Cl, 0.37-3.32) in the basal-like subgroup, which indicates a better outcome for patients in the HER-2 and basal-like subgroups who received HDCT The MMN cluster showed a trend to a better EFS after HDCT compared with DDCTConclusions: Protein expression profiling in high-risk breast cancers identified five subtypes, which differed with respect to survival and response to chemotherapy: In contrast to luminal-A and luminal-B subtypes, HER-2 and basal-like subgroups had a significant predictive benefit, and the MMN cluster had a trend to a predictive benefit, both from HDCT when compared with DDCT.