Rossing Maria, Sørensen Claus Storgaard, Ejlertsen Bent, Nielsen Finn Cilius
Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
APMIS. 2019 May;127(5):303-315. doi: 10.1111/apm.12920. Epub 2019 Jan 28.
Breast cancer was the first to take advantage of targeted therapy using endocrine therapy, and for up to 20% of all breast cancer patients a further significant improvement has been obtained by HER2-targeted therapy. Greater insight in precision medicine is to some extent driven by technical and computational progress, with the first wave of a true technical advancement being the application of transcriptomic analysis. Molecular subtyping further improved our understanding of breast cancer biology and has through a new tumor classification enabled allocation of personalized treatment regimens. The next wave in technical progression must be next-generation-sequencing which is currently providing new and exciting results. Large-scale sequencing data unravel novel somatic and potential targetable mutations as well as allowing the identification of new candidate genes predisposing for familial breast cancer. So far, around 15% of all breast cancer patients are genetically predisposed with most genes being factors in pathways implicated in genome maintenance. This review focuses on whole-genome sequencing and the new possibilities that this technique, together with other high-throughput analytic approaches, provides for a more individualized treatment course of breast cancer patients.
乳腺癌是首个利用内分泌疗法进行靶向治疗的癌症,对于高达20%的乳腺癌患者而言,HER2靶向治疗使其病情得到了进一步显著改善。对精准医学的更深入理解在一定程度上得益于技术和计算方面的进步,真正技术进步的第一波浪潮是转录组分析的应用。分子亚型分类进一步增进了我们对乳腺癌生物学的理解,并通过新的肿瘤分类实现了个性化治疗方案的分配。技术进步的下一波浪潮必定是新一代测序技术,目前它正在带来新的、令人振奋的成果。大规模测序数据揭示了新的体细胞突变和潜在的可靶向突变,还能识别出家族性乳腺癌的新候选基因。到目前为止,约15%的乳腺癌患者具有遗传易感性,其中大多数基因是参与基因组维持的信号通路中的因子。本综述聚焦于全基因组测序以及该技术与其他高通量分析方法一起为乳腺癌患者提供更个性化治疗方案的新可能性。