基底样和非基底样三阴性乳腺癌的分子特征。
Molecular characterization of basal-like and non-basal-like triple-negative breast cancer.
机构信息
Medical Oncology Department, Vall d’Hebron Institute of Oncology, Barcelona, Spain.
出版信息
Oncologist. 2013;18(2):123-33. doi: 10.1634/theoncologist.2012-0397. Epub 2013 Feb 12.
Triple-negative (TN) and basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormone receptors and overexpression and/or amplification of HER2. However, both classifications show substantial discordance rates when compared to each other. Here, we molecularly characterize TN tumors and BL tumors, comparing and contrasting the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 BL tumors, 21.4% and 31.5% were identified as non-BL and non-TN, respectively. TN tumors identified as luminal or HER2-enriched (HER2E) showed undistinguishable overall gene expression profiles when compared versus luminal or HER2E tumors that were not TN. Similar findings were observed within BL tumors regardless of their TN status, which suggests that molecular subtype is preserved regardless of individual marker results. Interestingly, most TN tumors identified as HER2E showed low HER2 expression and lacked HER2 amplification, despite the similar overall gene expression profiles to HER2E tumors that were clinically HER2-positive. Lastly, additional genomic classifications were examined within TN and BL cancers, most of which were highly concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.
三阴性(TN)和基底样(BL)乳腺癌的定义可以互换使用,以鉴定缺乏激素受体表达以及 HER2 过表达和/或扩增的乳腺癌。然而,当相互比较时,这两种分类都显示出相当大的不一致率。在这里,我们对 TN 肿瘤和 BL 肿瘤进行了分子特征分析,比较和对比了每种肿瘤的常见模式和独特模式的结果。在总共测试的 412 个 TN 肿瘤和 473 个 BL 肿瘤中,分别有 21.4%和 31.5%被鉴定为非 BL 和非 TN。与非 TN 的 luminal 或 HER2 富集(HER2E)肿瘤相比,被鉴定为 luminal 或 HER2E 的 TN 肿瘤显示出无差异的总体基因表达谱。在 BL 肿瘤中也观察到了类似的发现,无论其 TN 状态如何,这表明分子亚型是保留的,而与单个标志物结果无关。有趣的是,大多数被鉴定为 HER2E 的 TN 肿瘤表现出低 HER2 表达并且缺乏 HER2 扩增,尽管与临床 HER2 阳性的 HER2E 肿瘤具有相似的总体基因表达谱。最后,还在 TN 和 BL 癌症中检查了其他基因组分类,其中大多数与肿瘤内在亚型高度一致。这些结果表明,未来专注于 TN 疾病的临床试验应考虑根据 BL 与非 BL 基因表达谱对患者进行分层,这似乎是 TN 乳腺癌患者中看到的主要生物学差异。