Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
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DOI：
10.1038/nrclinonc.2016.66
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发表时间：
2016-11
期刊：
影响因子：
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通讯作者：
Gianni L
中科院分区：
文献类型：
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作者：
Bianchini G;Balko JM;Mayer IA;Sanders ME;Gianni L
化疗是三阴性乳腺癌（TNBC）患者在疾病早期和晚期的主要系统性治疗。靶向治疗的缺乏和TNBC患者的不良预后促进了发现可操作的分子靶点以治疗这些肿瘤患者的重大努力。大规模平行测序和其他“组学”技术揭示了TNBC的非预期异质性水平，并导致在一些TNBC中鉴定出潜在的可操作分子特征，如生殖系BRCA 1/2突变或“BRCAness”，雄激素受体的存在和几种罕见的基因组改变。然而，这些改变是否是分子“驱动器”尚未明确确定。一个亚组的TNBC显示出高度的肿瘤浸润淋巴细胞，这也与较低的疾病复发风险和较高的化疗获益可能性相关。在晚期TNBC中使用免疫检查点抑制剂的原理验证研究已经取得了令人鼓舞的结果，表明免疫治疗对TNBC患者的潜在益处。在这篇综述中，我们讨论了过去十年中TNBC中最相关的分子发现以及从这些数据中获得的最有希望的治疗机会。
Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other ‘omics’ technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or ‘BRCAness’, the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular ‘drivers’, however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.