Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes
Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes
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DOI：
10.1158/1078-0432.ccr-08-2132
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发表时间：
2009-04-01
影响因子：
11.5
通讯作者：
Ellis, Ian O.
中科院分区：
文献类型：
--
作者：
Rakha, Emad A.;Elsheikh, Somaia E.;Ellis, Ian O.
目的：三阴性（TN；雌激素受体、孕激素受体和 HER-2 阴性）癌症和基底样乳腺癌 (BLBC) 与不良预后相关，并且缺乏靶向治疗的益处。人们普遍认为 BLBC 和 TN 肿瘤是同义词，并且可以使用 TN 定义来定义 BLBC，无需表达基础标志物。 实验设计：我们使用了两个明确定义的乳腺癌队列，其中包含大量生物标志物、BRCA1 突变状态和随访数据，以比较表达一种或多种以下各项的 TN 肿瘤的临床病理学和免疫组织化学特征： 特定基础标记物（CK5/6、CK17、CK14 和表皮生长因子受体；BLBC）与不表达这些标记物的 TN 肿瘤（TN3BKE-）进行比较。结果：在此，我们表明，虽然 BLBC 的形态学特征与 TN3BKE- 肿瘤没有显着差异，但 BLBC 显示出明显的临床和免疫表型差异。 BLBC 与缺氧相关因子 (CA9)、神经内分泌标记物和其他不良预后标记物（如 p53）的表达存在统计学显着相关性。细胞周期相关蛋白和涉及肿瘤免疫学特征的生物标志物的表达存在差异。与TN3BKE-肿瘤相比，BLBC与BRCA1突变状态呈正相关，并表现出独特的远处转移模式、对化疗的更好反应和更短的生存期。结论：TN乳腺癌包含一组非常异质的肿瘤。基础标记物的表达可识别 TN 肿瘤的生物学和临床上不同的亚组，证明使用基础标记物（在 TN 肿瘤中）来定义 BLBC 是合理的。
Purpose: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers.Experimental Design: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-).Results: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival.Conclusion: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.