Olopade Olufunmilayo I, Grushko Tatyana A, Nanda Rita, Huo Dezheng
Department of Medicine, Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois 60637, USA.
Clin Cancer Res. 2008 Dec 15;14(24):7988-99. doi: 10.1158/1078-0432.CCR-08-1211.
Breast cancer is a complex disease caused by the progressive accumulation of multiple gene mutations combined with epigenetic dysregulation of critical genes and protein pathways. There is substantial interindividual variability in both the age at diagnosis and phenotypic expression of the disease. With an estimated 1,152,161 new breast cancer cases diagnosed worldwide per year, cancer control efforts in the postgenome era should be focused at both population and individual levels to develop novel risk assessment and treatment strategies that will further reduce the morbidity and mortality associated with the disease. The discovery that mutations in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancers has radically transformed our understanding of the genetic basis of breast cancer, leading to improved management of high-risk women. A better understanding of tumor host biology has led to improvements in the multidisciplinary management of breast cancer, and traditional pathologic evaluation is being complemented by more sophisticated genomic approaches. A number of genomic biomarkers have been developed for clinical use, and increasingly, pharmacogenetic end points are being incorporated into clinical trial design. For women diagnosed with breast cancer, prognostic or predictive information is most useful when coupled with targeted therapeutic approaches, very few of which exist for women with triple-negative breast cancer or those with tumors resistant to chemotherapy. The immediate challenge is to learn how to use the molecular characteristics of an individual and their tumor to improve detection and treatment, and ultimately to prevent the development of breast cancer. The five articles in this edition of CCR Focus highlight recent advances and future directions on the pathway to individualized approaches for the early detection, treatment, and prevention of breast cancer.
乳腺癌是一种复杂的疾病，由多种基因突变的逐步积累以及关键基因和蛋白质通路的表观遗传失调所致。该疾病在诊断年龄和表型表达方面存在显著的个体差异。据估计，全球每年有1,152,161例新发乳腺癌病例，后基因组时代的癌症防控工作应聚焦于人群和个体层面，以制定新的风险评估和治疗策略，进一步降低与该疾病相关的发病率和死亡率。BRCA1和BRCA2基因的突变会增加患乳腺癌和卵巢癌风险这一发现，彻底改变了我们对乳腺癌遗传基础的理解，从而改善了对高危女性的管理。对肿瘤宿主生物学的更深入了解促进了乳腺癌多学科管理的改善，传统病理评估正得到更精密的基因组方法的补充。一些基因组生物标志物已被开发用于临床，并且越来越多的药物遗传学终点正被纳入临床试验设计。对于被诊断为乳腺癌的女性，预后或预测信息与靶向治疗方法相结合时最为有用，但三阴性乳腺癌患者或对化疗耐药的肿瘤患者可用的靶向治疗方法极少。当前的挑战是要学会如何利用个体及其肿瘤的分子特征来改善检测和治疗，并最终预防乳腺癌的发生。本期《临床癌症研究聚焦》中的五篇文章重点介绍了在乳腺癌早期检测、治疗和预防的个体化方法之路上的最新进展和未来方向。
