Curigliano Giuseppe
Division of Experimental Cancer Medicine, Istituto Europeo di Oncologia, Milano, Italy.
Handb Exp Pharmacol. 2018;249:289-297. doi: 10.1007/164_2018_147.
New experimental breast cancer therapies directed against novel targets are currently in clinical These experimental agents are likely to be effective for a niche of breast cancers with specific "driver mutations". The ability to perform comprehensive molecular profiling of individual tumors has rapidly expanded over the last few years, and new DNA sequencing technologies require relatively limited quantities of fresh or archived paraffin-embedded or snap-frozen tumor tissue and provide rapid turnaround of sequencing results within a few weeks or less. All these technologies provide an unprecedented opportunity to identify patients with rare "driver" molecular alternations that are candidates for proof-of-concept clinical trials with matched targeted therapy, in the context of basket trials. The aim of this chapter on molecular profiling is to summarize the known recurrent molecular alterations in breast cancer that are potentially amenable to investigational targeted therapy, to provide an overview of the existing technological platforms for molecular profiling and ongoing or planned institutional/national screening initiatives and to outline a vision for molecular screening that may be integrated into the future activities of breast cancer research.
目前，针对新靶点的新型实验性乳腺癌疗法正处于临床阶段。这些实验性药物可能对具有特定“驱动突变”的一部分乳腺癌有效。在过去几年中，对个体肿瘤进行全面分子分析的能力迅速发展，新的DNA测序技术所需的新鲜或存档的石蜡包埋或速冻肿瘤组织量相对有限，并能在几周或更短时间内快速给出测序结果。在篮子试验的背景下，所有这些技术都提供了前所未有的机会，来识别那些具有罕见“驱动”分子改变的患者，这些患者是进行匹配靶向治疗的概念验证临床试验的候选者。本章关于分子分析的目的是总结乳腺癌中已知的、可能适用于研究性靶向治疗的复发性分子改变，概述现有的分子分析技术平台以及正在进行或计划中的机构/国家筛查计划，并勾勒出一个可能整合到未来乳腺癌研究活动中的分子筛查愿景。
