Triple negative breast cancers (TNBCs) represent 10%-20% of primary breast cancers, and despite having greater initial sensitivity to cytotoxic chemotherapy, patients with TNBCs have higher rates of distant metastasis and a poorer prognosis compared with patients with hormone receptor positive and/or human epidermal growth factor receptor 2 positive disease. TNBC has historically been treated as a single disease entity in targeted therapy trials, but advances in gene expression profiling and other molecular diagnostic techniques over the last decade have revealed considerable biologic heterogeneity within TNBCs, including subgroups with distinct, targetable aberrations. Such molecular heterogeneity explains, in part, the disappointing performance of targeted therapeutics in unselected TNBC. Here we discuss the history of gene expression profiling in breast cancer and its application in partitioning TNBCs into subtypes that may lead to more consistent therapeutic successes in this heterogeneous disease.
Implications for practice: Triple negative breast cancers (TNBCs) have historically been regarded as a single entity in clinical trial design. Over the last decade, molecular characterization has revealed much heterogeneity in TNBCs, explaining in part the lackluster performance of targeted therapeutics in TNBCs as a group. In this article, we review the history of the molecular classification of breast cancer based on gene expression profiling and discuss its role in TNBCs.
摘要
三阴性乳腺癌（TNBC）占原发性乳腺癌的10%‐20%。虽然与激素受体阳性和/或人表皮生长因子受体2阳性疾病患者相比, TNBC患者对细胞毒性化疗的初始敏感性更大, 但其远端转移的发生率也更高并且预后更差。在以往的靶向治疗试验中, TNBC被视作单一病种。过去十年中基因表达谱和其它分子诊断技术的进步表明TNBC具有相当大的生物学异质性, 包括靶向畸变明显不同的亚组。这种分子异质性部分地解释了非选择性TNBC中靶向治疗令人失望的原因。在本文中, 我们讨论了乳腺癌中基因表达谱的历史及其在将TNBC分成可能使这种异质性疾病的治疗更成功的亚型中的应用。
Keywords: Gene expression profiling; Molecular subtypes; Targeted therapy; Triple negative breast cancer.
© AlphaMed Press 2017.