Circulating tumor cells and plasma DNA analysis in patients with indeterminate early or metastatic breast cancer

Circulating tumor cells and plasma DNA analysis in patients with indeterminate early or metastatic breast cancer
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DOI:
10.2217/bmm.10.118
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发表时间:
2011-02-01
影响因子:
2.2
通讯作者:
Stebbing, Justin
Stebbing, Justin
中科院分区:
医学4区
文献类型:
--
作者:
Shaw, Jacqui A.;Brown, James;Stebbing, Justin

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背景资料:循环肿瘤细胞(CTC)和无细胞血浆DNA中的肿瘤特异性改变都可以用作乳腺癌预后的标志物。到目前为止,还没有研究将这些作为早期乳腺癌随访中亚临床转移的标志物进行比较。在这项研究中,我们测量了一组已发表的多发性肺结节和不确定转移性疾病患者的CTC和血浆DNA。患者和方法:手术后约1.5年,从19名经组织学证实患有原发性乳腺癌和肺小结节的女性中采集用于CTC和血浆DNA测量的单一血液样本。CellSearch系统用于富集和计数来自外周血的CTC。从血浆中分离DNA,并通过定量实时PCR分析DNA浓度、完整性和HER2扩增的证据。结果如下:在19名患有“不确定”早期或转移性乳腺癌的个体中,17名没有表现出CTC的证据,一名有一个CTC,一名有三个CTC。平均血浆DNA浓度较低,且在健康女性对照组中检出的范围内,DNA完整性值也是如此。在8例HER2免疫组化3+肿瘤患者中的4例中,在血浆DNA中检测到HER2扩增,但与2例CTC阳性患者没有重叠。到目前为止,没有患者复发(中位随访时间:3.5年)。结论:CTC和血浆DNA分析共同提示这些患者几乎没有转移性疾病的证据。未来的研究将被设计为评估这些生物标志物在大量乳腺癌女性随访中的效用。
Background: Circulating tumor cells (CTCs) and tumor-specific alterations in cell-free plasma DNA can both be used as markers of prognosis in breast cancer. To date, there have been no studies that have compared these as markers for subclinical metastases in the follow-up of early breast cancer. In this study, we measured CTCs and plasma DNA in a published group of patients with multiple pulmonary nodules and indeterminate metastatic disease. Patients & methods: A single blood sample for CTC and plasma DNA measurement was taken approximately 1.5 years after surgery from 19 women with histologically confirmed primary breast cancer and small pulmonary nodules. The CellSearch system was used to enrich and enumerate CTCs from peripheral blood. DNA was isolated from plasma and was analyzed by quantitative real-time PCR for DNA concentration, integrity and evidence of HER2 amplification. Results: Of the 19 individuals with 'indeterminate' early or metastatic breast cancer, 17 demonstrated no evidence of CTCs, one had one CTC and one had three CTCs. The mean plasma DNA concentration was low and within the range detected in healthy female controls, as were the values for DNA integrity. HER2 amplification was detected in the plasma DNA in four of the eight patients with HER2 immunohistochemistry 3+ tumors, but there was no overlap with the two CTC-positive patients. None of the patients have relapsed thus far (median follow-up: 3.5 years). Conclusion: Both CTC and plasma DNA analyses together suggested that these patients had little evidence of metastatic disease. Future studies will be designed to assess the utility of these biomarkers in the follow-up of a larger number of women with breast cancer.