Le Du Fanny, Eckhardt Bedrich L, Lim Bora, Litton Jennifer K, Moulder Stacy, Meric-Bernstam Funda, Gonzalez-Angulo Ana M, Ueno Naoto T
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Oncology, Eugène Marquis Cancer Center, Rennes, France.
Oncotarget. 2015 May 30;6(15):12890-908. doi: 10.18632/oncotarget.3849.
Significant research has been conducted to better understand the extensive, heterogeneous molecular features of triple-negative breast cancer (TNBC). We reviewed published TNBC molecular classifications to identify major groupings that have potential for clinical trial development. With the ultimate aim to streamline translational medicine, we linked these categories of TNBC according to their gene-expression signatures, biological function, and clinical outcome. To this end, we define five potential clinically actionable groupings of TNBC: 1) basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2) mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem cell features; 3) immune-associated TNBC; 4) luminal/apocrine TNBC with androgen-receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we highlight the major biological pathways and discuss potential targeted therapies in TNBC that might abrogate disease progression. However, many of these potential targets need clinical validation by clinical trials. We have yet to know how we can enrich the targets by molecular classifications.
为了更好地理解三阴性乳腺癌（TNBC）广泛的、异质性的分子特征，已经开展了大量研究。我们回顾了已发表的TNBC分子分类，以确定具有临床试验开发潜力的主要分组。为了最终简化转化医学，我们根据TNBC的基因表达特征、生物学功能和临床结果将这些类别联系起来。为此，我们定义了TNBC的五个潜在临床可操作分组：1）具有DNA修复缺陷或生长因子途径的基底样TNBC；2）具有上皮-间质转化和癌症干细胞特征的间质样TNBC；3）免疫相关TNBC；4）雄激素受体过表达的管腔/大汗腺TNBC；5）HER2富集TNBC。对于每个定义的亚型，我们强调主要的生物学途径，并讨论可能消除疾病进展的TNBC潜在靶向治疗。然而，许多这些潜在靶点需要通过临床试验进行临床验证。我们尚不清楚如何通过分子分类来富集靶点。
