Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
复制标题
DOI：
10.1056/nejmoa1213261
复制
发表时间：
2013-03-28
影响因子：
158.5
通讯作者：
Rosenfeld, Nitzan
中科院分区：
文献类型：
--
作者：
Dawson, Sarah-Jane;Tsui, Dana W. Y.;Rosenfeld, Nitzan
背景转移性乳腺癌的治疗需要监测肿瘤负荷以确定对治疗的反应，并且需要改进生物标志物。肿瘤抗原15-3 （CA 15-3）和循环肿瘤细胞等生物标志物已被广泛研究。然而，携带肿瘤特异性改变的循环无细胞DNA（循环肿瘤DNA）尚未被广泛研究或与乳腺癌中的其他循环生物标志物进行比较。方法对30例接受全身治疗的转移性乳腺癌患者的肿瘤x线影像与循环肿瘤DNA、CA 15-3和循环肿瘤细胞的测定进行比较。我们使用靶向或全基因组测序来鉴定体细胞基因组改变，并设计个性化检测来量化连续收集的血浆标本中的循环肿瘤DNA。在相同的时间点测量CA 15-3水平和循环肿瘤细胞数量。结果30例女性中29例（97%）成功检出循环肿瘤DNA，其中体细胞基因组改变；27名女性中有21名（78%）和30名女性中有26名（87%）检测到CA 15-3和循环肿瘤细胞。与CA 15-3或循环肿瘤细胞相比，循环肿瘤DNA水平表现出更大的动态范围，与肿瘤负荷变化的相关性更大。在测试的措施中，循环肿瘤DNA为19名妇女中的10名（53%）提供了最早的治疗反应措施。结论：这一概念验证分析表明，循环肿瘤DNA是一种信息丰富、固有特异性强、高度敏感的转移性乳腺癌生物标志物。（由英国癌症研究中心和其他机构资助。）
BACKGROUNDThe management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment, and improved biomarkers are needed. Biomarkers such as cancer antigen 15-3 (CA 15-3) and circulating tumor cells have been widely studied. However, circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA) has not been extensively investigated or compared with other circulating biomarkers in breast cancer.METHODSWe compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy. We used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. CA 15-3 levels and numbers of circulating tumor cells were measured at identical time points.RESULTSCirculating tumor DNA was successfully detected in 29 of the 30 women (97%) in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women (78%) and 26 of 30 women (87%), respectively. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53%).CONCLUSIONSThis proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. (Funded by Cancer Research UK and others.)