Goldberg Jessica I, Borgen Patrick I
Breast Service, Memorial Sloan Kettering Cancer Center Department of Surgery, 1275 York Avenue, MRI-1026, New York, NY 10021, USA.
Expert Rev Anticancer Ther. 2006 Aug;6(8):1205-14. doi: 10.1586/14737140.6.8.1205.
Breast cancer is a genetic disease. The cancer phenotype is defined by a complex interplay between oncogenes, tumor-suppressor genes and epigenetic factors. Only 5-10% of all breast cancers can be attributed to one of several breast cancer familial syndromes, the most common of which is the hereditary breast and ovarian syndrome caused by deleterious mutations of the BRCA1 or BRCA2 tumor-suppressor genes. The functions of the BRCA proteins are not fully understood, although it is clear that they play a role in the control of transcription, regulation of the cell cycle and management of DNA damage. The inheritance of a deleterious BRCA mutation is accompanied by a 50-80% risk of developing breast cancer, 60% risk of developing a contralateral breast cancer and 15-25% risk of developing ovarian cancer. The clinical management of BRCA heterozygotes involves several strategies of primary, secondary and tertiary prevention. These include risk-reducing surgery, chemoprevention, lifestyle changes and increased surveillance. As we move beyond the 10-year anniversary of the discovery of the BRCA genes, we are inevitably led to thoughtful reflection on the impact of these genes in regards to the greater problem of sporadic breast cancer.
乳腺癌是一种遗传性疾病。癌症表型由癌基因、肿瘤抑制基因和表观遗传因素之间的复杂相互作用所定义。在所有乳腺癌中，只有5%-10%可归因于几种乳腺癌家族综合征之一，其中最常见的是由BRCA1或BRCA2肿瘤抑制基因的有害突变引起的遗传性乳腺癌和卵巢综合征。尽管很明显BRCA蛋白在转录控制、细胞周期调节和DNA损伤管理中发挥作用，但其功能尚未完全了解。携带有害BRCA突变会有50%-80%的患乳腺癌风险、60%的患对侧乳腺癌风险以及15%-25%的患卵巢癌风险。BRCA杂合子的临床管理涉及一级、二级和三级预防的多种策略。这些策略包括降低风险的手术、化学预防、生活方式改变和加强监测。随着我们迎来BRCA基因发现10周年，我们不可避免地要深入思考这些基因对散发性乳腺癌这一更大问题的影响。
