How basal are triple-negative breast cancers?
How basal are triple-negative breast cancers?
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DOI：
10.1002/ijc.23518
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发表时间：
2008-07-01
影响因子：
6.4
通讯作者：
Birnbaum, Daniel
中科院分区：
文献类型：
--
作者：
Bertucci, Francois;Finetti, Pascal;Birnbaum, Daniel
乳腺癌（BC）的基础分子亚型由与500个基因集内在相似的mRNA表达模式定义。它是转录方面最同质的亚型，也是预后方面最具侵略性的亚型之一。已经在基础BC中启动了测试新的全身治疗策略的临床试验。尽管尚未报告证据，但在这些试验中，基底肿瘤目前被同化并选择为三阴性（TN）BC，因为它们对激素和ERBB 2受体的免疫组化（IHC）频繁呈阴性。在这里，我们评估了TN表型（基于IHC的定义）和基础亚型（基于基因表达的定义）的相关性和同质性程度。我们分析了172例根据基因表达谱定义为基底（123例）和非基底（49例）的TN BC。相反，160个肿瘤根据其基因表达谱被定义为基底，包括123个TN和37个非TN样本。单因素和多因素分析显示，TN BC代表了比基底BC更异质的组，包括在组织临床和分子水平上非常不同的基底和非基底肿瘤，特别是在临床试验中评估的特定疗法靶向的分子的mRNA表达。这些结果要求在解释正在进行的试验和在未来的试验中选择患者时要谨慎。它们还保证了比基因表达谱更适用于临床的基础BC的分子标记物的鉴定。(C)2008 Wilcy-Liss，Inc.
The basal molecular subtype of breast cancer (BC) is defined by the mRNA expression pattern of an intrinsic similar to 500-gene set. It is the most homogeneous subtype in transcriptional terms, and one of the most aggressive in prognostic terms. Clinical trials testing new systemic therapeutic strategies have been launched in basal BCs. Although no proof of evidence has yet been reported, basal tumors are currently assimilated to and selected as triple-negative (TN) BCs in these trials because of their frequent immunohistochemical (IHC) negativity for hormone and ERBB2 receptors. Here, we have assessed the degrees of correlation and of homogeneity of the TN phenotype (IHC-based definition) and the basal subtype (gene expression-based definition). We analyzed 172 TN BCs defined by gene expression profile as basal (123 cases) and nonbasal (49 cases). Conversely, 160 tumors were defined as basal by their gene expression profile and included 123 TN and 37 non-TN samples. Uni- and multivariate analyses revealed that TN BCs represent a more heterogeneous group than basal BCs, including basal and nonbasal tumors very different both at the histoclinical and molecular level, notably for mRNA expression of molecules targeted by specific therapies under evaluation in clinical trials. These results call for caution in the interpretation of ongoing trials and selection of patients in future trials. They also warrant the identification of molecular markers for basal BCs more clinically applicable than gene expression profiles. (C) 2008 Wilcy-Liss, Inc.