乳腺癌液体活检的现状与前景

Current situation and prospect of breast cancer liquid biopsy

液体活检是通过体液标本进行诊断分析的检测方法，检测标本主要包括外周血、尿液、唾液、胸腹腔积液等，肿瘤诊治是其主要应用领域。与传统组织活检相比，液体活检具有创伤小、取材方便、易重复采集的特点。循环肿瘤细胞和循环肿瘤DNA（ctDNA）检测是目前液体活检的主要方式。ctDNA对检测技术要求高，二代测序和数字PCR技术的进步推动了ctDNA检测相关研究的进程。2016年Nature发表了乳腺癌全基因组测序的研究成果。发现93个可能与乳腺癌发生相关的蛋白编码基因的1628个突变，为乳腺癌ctDNA检测研究提供了新的平台。近年来，根据ctDNA检测监测临床疗效并指导治疗的临床研究已有报道。二代测序技术在全面反映肿瘤遗传信息，指导靶向治疗方面更具优势，但利用二代测序技术检测ctDNA仍处在研究阶段。推动检测技术规范化，开展前瞻性临床试验加以验证至关重要，大规模用于指导乳腺癌临床实践时机仍不成熟。

Liquid biopsy is a diagnostic approach by analyzing body fluid samples. Peripheral blood is the most common sample. Urine, saliva, pleural effusion and ascites are also used. Now liquid biopsy is mainly used in the area of neoplasm diagnosis and treatment. Compared with traditional tissue biopsy, liquid biopsy is minimally invasive, convenient to sample and easy to repeat. Liquid biopsy mainly includes circulating tumor cells and circulating tumor DNA （ctDNA） detection. Detection of ctDNA requires sensitive and accurate methods. The progression of next-generation sequencing （NGS） and digital PCR promote the process of studies in ctDNA. In 2016,Nature published the result of whole-genome sequencing study of breast cancer. The study found 1 628 mutations of 93 protein-coding genes which may be driver mutations of breast cancer. The result of this study provided a new platform for breast cancer ctDNA studies. In recent years, there were many studies using etDNA detection to monitor therapeutic effect and guide treatment. NGS is a promising technique in accessing genetic information and guiding targeted therapy. It must be emphasized that ctDNA detection using NGS is still at research stage. It is important to standardize ctDNA detection technique and perform prospective clinical researches. The time is not ripe for using etDNA detection to guide large-scale breast cancer clinical practice at present.