Guillem José G, Wood William C, Moley Jeffrey F, Berchuck Andrew, Karlan Beth Y, Mutch David G, Gagel Robert F, Weitzel Jeffrey, Morrow Monica, Weber Barbara L, Giardiello Francis, Rodriguez-Bigas Miguel A, Church James, Gruber Stephen, Offit Kenneth
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 2006 Oct 1;24(28):4642-60. doi: 10.1200/JCO.2005.04.5260.
Although the etiology of solid cancers is multifactorial, with environmental and genetic factors playing a variable role, a significant portion of the burden of cancer is accounted for by a heritable component. Increasingly, the heritable component of cancer predispositions has been linked to mutations in specific genes, and clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutations carriers for highly penetrant syndromes such as multiple endocrine neoplasias, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary breast and ovarian cancer syndromes are primarily surgical. For that reason, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) have undertaken an educational effort within the oncology community. A joint ASCO/SSO Task Force was charged with presenting an educational symposium on the surgical management of hereditary cancer syndromes at the annual ASCO and SSO meetings, resulting in an educational position article on this topic. Both the content of the symposium and the article were developed as a consensus statement by the Task Force, with the intent of summarizing the current standard of care. This article is divided into four sections addressing breast, colorectal, ovarian and endometrial cancers, and multiple endocrine neoplasia. For each, a brief introduction on the genetics and natural history of the disease is provided, followed by a detailed description of modern surgical approaches, including a description of the clinical and genetic indications and timing of prophylactic surgery, and the efficacy of prophylactic surgery when known. Although a number of recent reviews have addressed the role of genetic testing for cancer susceptibility, including the richly illustrated Cancer Genetics and Cancer Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group (available through http://www.asco.org), this article focuses on the issues surrounding the why, how, and when of surgical prophylaxis for inherited forms of cancer. This is a complex process, which requires a clear understanding of the natural history of the disease and variance of penetrance, a realistic appreciation of the potential benefit and risk of a risk-reducing procedure in a potentially otherwise healthy individual, the long-term sequelae of such surgical intervention, as well as the individual patient and family's perception of surgical risk and anticipated benefit.
尽管实体癌的病因是多因素的，环境和遗传因素发挥着不同作用，但癌症负担的很大一部分是由遗传因素造成的。越来越多的癌症易感性遗传因素与特定基因的突变有关，并且已经为受影响家族中的突变携带者制定了临床干预措施。对于高外显率综合征（如多发性内分泌腺瘤、家族性腺瘤性息肉病、遗传性非息肉病性结直肠癌以及遗传性乳腺癌和卵巢癌综合征）的突变携带者，主要干预措施是手术。因此，美国临床肿瘤学会（ASCO）和外科肿瘤学会（SSO）在肿瘤学界开展了一项教育工作。一个ASCO/SSO联合特别工作组负责在ASCO和SSO年度会议上举办关于遗传性癌症综合征外科治疗的教育研讨会，并就此主题撰写一篇教育立场文章。研讨会的内容和文章均由特别工作组制定为共识声明，旨在总结当前的护理标准。本文分为四个部分，分别涉及乳腺癌、结直肠癌、卵巢癌和子宫内膜癌以及多发性内分泌腺瘤。对于每种癌症，先简要介绍疾病的遗传学和自然史，然后详细描述现代手术方法，包括预防性手术的临床和遗传指征、时机，以及已知情况下预防性手术的疗效。尽管最近有一些综述探讨了癌症易感性基因检测的作用，包括ASCO癌症遗传学工作组内容丰富且配有大量插图的《癌症遗传学与癌症易感性检测课程》（可通过http://www.asco.org获取），但本文重点关注遗传性癌症手术预防的原因、方法和时机等问题。这是一个复杂的过程，需要清楚了解疾病的自然史和外显率差异，切实认识到在潜在健康个体中进行降低风险手术的潜在益处和风险、此类手术干预的长期后遗症，以及患者个体和家庭对手术风险和预期益处的认知。
