Molecular alterations in triple-negative breast cancer-the road to new treatment strategies
Molecular alterations in triple-negative breast cancer-the road to new treatment strategies
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DOI：
10.1016/s0140-6736(16)32454-0
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发表时间：
2017-06-17
期刊：
影响因子：
168.9
通讯作者：
von Minckwitz, Gunter
中科院分区：
文献类型：
--
作者：
Denkert, Carsten;Liedtke, Cornelia;von Minckwitz, Gunter
三阴性乳腺癌是一种异质性疾病，长期以来一直没有特定的治疗方法。因此，常规化疗仍然被认为是最先进的临床状态。三阴性乳腺癌的不同亚组已经根据蛋白质表达、mRNA特征和基因组改变进行了鉴定。三阴性乳腺癌生物学的重要因素包括高增殖活性、增加的免疫浸润、基底样和间充质表型以及同源重组缺陷，其部分与BRCA 1或BRCA 2功能丧失相关。少数三阴性肿瘤表达管腔标记物，如雄激素受体，并具有较低的增殖活性。这些生物学亚组是重叠的，目前不能组合成一个统一的三阴性乳腺癌生物学模型。然而，对这种疾病的分子分析已经确定了靶向治疗干预的潜在选择。这导致了有希望的临床策略，包括靶向DNA损伤反应的改良化疗方法，血管生成抑制剂，免疫检查点抑制剂，甚至抗雄激素，所有这些都在1-3期临床研究中进行评估。本系列论文重点关注最相关的临床问题，总结了最近的临床试验结果，并概述了正在进行的研究和试验概念，这些研究和试验概念将为这种肿瘤类型提供更精细的治疗。
Triple-negative breast cancer is a heterogeneous disease and specific therapies have not been available for a long time. Therefore, conventional chemotherapy is still considered the clinical state of the art. Different subgroups of triple-negative breast cancer have been identified on the basis of protein expression, mRNA signatures, and genomic alterations. Important elements of triple-negative breast cancer biology include high proliferative activity, an increased immunological infiltrate, a basal-like and a mesenchymal phenotype, and deficiency in homologous recombination, which is in part associated with loss of BRCA1 or BRCA2 function. A minority of triple-negative tumours express luminal markers, such as androgen receptors, and have a lower proliferative activity. These biological subgroups are overlapping and currently cannot be combined into a unified model of triple-negative breast cancer biology. Nevertheless, the molecular analysis of this disease has identified potential options for targeted therapeutic intervention. This has led to promising clinical strategies, including modified chemotherapy approaches targeting the DNA damage response, angiogenesis inhibitors, immune checkpoint inhibitors, or even anti-androgens, all of which are being evaluated in phase 1-3 clinical studies. This Series paper focuses on the most relevant clinical questions, summarises the results of recent clinical trials, and gives an overview of ongoing studies and trial concepts that will lead to a more refined therapy for this tumour type.