Division of Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, II Policlinico via S. Pansini, 5, 80131, Naples, Italy.
Curr Oncol Rep. 2018 Aug 20;20(10):76. doi: 10.1007/s11912-018-0726-6.
Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients.
Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups. Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.
三阴性乳腺癌(TNBC)占诊断出的乳腺癌的 15-20%,在年轻和非裔美国女性中发病率更高,并且常与 BRCA 种系突变有关。在疾病的早期和晚期阶段,化疗是唯一经过充分验证的治疗选择。与基于蒽环类药物和/或紫杉烷的标准化疗治疗相比,TNBC 肿瘤在标准治疗后更早复发,通常在诊断后 1-3 年内,并且经常发生内脏转移,是所有乳腺癌中预后最差的亚型。在本综述中,我们将提供该疾病最近临床试验的最新结果概述,并描述已知分子途径的意义,这些途径代表了为 TNBC 患者开发未来治疗方法的新靶点。
在过去十年中,基因表达微阵列技术的出现导致了不同可操作靶点的鉴定,包括各种基因组改变、雄激素受体、PARP、PI3K、VEGF 和血管生成途径的其他蛋白质。因此,新型靶向药物已在临床试验中进行了测试,这些试验报告了特定 TNBC 分子亚组中的有希望的结果。尽管细胞毒性化疗仍然是 TNBC 患者治疗的主要方法,但鉴定新的“可治疗”靶点和途径以开发个性化治疗方法代表了管理 TNBC 亚型的一种很有前途的研究方法。