Ziogas Dimosthenis, Roukos Dimitrios H
Department of Surgery, Ioannina University School of Medicine, Ioannina, Greece.
Ann Surg Oncol. 2009 Jul;16(7):1771-82. doi: 10.1245/s10434-009-0436-2. Epub 2009 Mar 26.
The age of personal genomics is here. A flood of translational research discoveries may influence also surgeon oncologist. Breast-conserving surgery (BCS) is standard care in early breast cancer. Classic clinicopathologic factors are suboptimal to predict risk of ipsilateral breast cancer (IBC) recurrence and/or contralateral breast cancer (CBC). Human genetic variation may be involved in local failures.
To describe the potential clinical utility of genetics, personal genomics, and epigenetics to identify IBC/CBC high-risk patients who might benefit from aggressive surgery (bilateral mastectomy).
PubMed (MEDLINE) was searched (January 1990 to November 2008).
Even following current guidelines, IBC/CBC as isolated first event in a long-term aspect after treatment suggests a serious problem. Preclinical and clinical data reveal that at highest risk of IBC/CBC are patients with inherited BRCA1/2 mutations who benefited from bilateral mastectomy. Local failure risk prediction is currently unfeasible among familial non-BRCA1/2 (BRCA-test negative) and sporadic (no family history) breast cancer. Genome-wide association studies have already identified novel risk alleles with a series of tumor-initiating single-nucleotide polymorphisms (SNPs). Some of these variants and other novel SNPs and copy-number variants (CNVs) may also be relevant for local failures (IBC/CBC).
Beyond established risk factors, genetic testing allows identification of high-risk patients (BRCA mutation carriers) who may benefit from bilateral mastectomy rather than BCS. Human genetic variation (SNPs/CNVs) and DNA methylation may be relevant for local failures assessment. Technological revolution has opened a new avenue but multiple challenges should be overcome to integrate SNPs/CNVs as markers for IBC/CBC risk-stratification-based personalized surgery.
个人基因组学时代已然来临。大量的转化研究发现可能也会影响外科肿瘤学家。保乳手术（BCS）是早期乳腺癌的标准治疗方法。经典的临床病理因素在预测同侧乳腺癌（IBC）复发和/或对侧乳腺癌（CBC）风险方面并不理想。人类基因变异可能与局部复发有关。
描述遗传学、个人基因组学和表观遗传学在识别可能从积极手术（双侧乳房切除术）中获益的IBC/CBC高危患者方面的潜在临床应用价值。
检索了PubMed（MEDLINE，1990年1月至2008年11月）。
即使遵循当前指南，从长期来看，IBC/CBC作为治疗后的孤立首发事件仍表明存在严重问题。临床前和临床数据显示，IBC/CBC风险最高的是携带遗传性BRCA1/2突变的患者，他们从双侧乳房切除术中获益。目前，在家族性非BRCA1/2（BRCA检测阴性）和散发性（无家族史）乳腺癌中，局部复发风险预测尚不可行。全基因组关联研究已经确定了一系列与肿瘤起始单核苷酸多态性（SNP）相关的新风险等位基因。其中一些变异以及其他新的SNP和拷贝数变异（CNV）可能也与局部复发（IBC/CBC）有关。
除了既定的风险因素外，基因检测能够识别出可能从双侧乳房切除术而非保乳手术中获益的高危患者（BRCA突变携带者）。人类基因变异（SNP/CNV）和DNA甲基化可能与局部复发评估有关。技术革命开辟了一条新途径，但要将SNP/CNV整合为基于IBC/CBC风险分层的个性化手术的标志物，还需克服诸多挑战。
