HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients
HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients
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DOI：
10.1158/1078-0432.ccr-05-2087
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Brandt, B
中科院分区：
文献类型：
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作者：
Wülfing, P;Borchard, J;Brandt, B
目的：淋巴结阴性乳腺癌的早期转移表明乳腺癌细胞明显可以绕过淋巴结直接向远处器官血行播散。为此，我们评估了42例乳腺癌患者外周血中的血源性、HER 2阳性循环肿瘤细胞（CTC）的预后价值，中位随访时间为95 months.Experimental Design：通过专利的浮力密度梯度和免疫磁性分离相结合的方法分离细胞，并通过免疫细胞化学进行分析。我们在35例无明显转移的患者中的17例（48.6%）的外周血中检测到1 - 8个CTC。作为阳性对照，7例（100%）转移性疾病患者中有7例呈阳性。健康人和非恶性疾病手术患者（n = 32）CTC呈阴性。HER 2阳性CTC的存在和频率与无病生存率（P < 0.005）和总生存率（P < 0.05）显著降低相关。有趣的是，在12例HER 2阳性CTCs，原发性肿瘤是阴性HER 2免疫组化评分和荧光原位hybridization.Conclusions评估：这项研究提供了一些证据的HER 2阳性CTCs在I期至III期乳腺癌的预后影响。未来的研究必须确定接受HER 2靶向治疗的患者在HER 2阳性CTC水平方面的结局，因为高水平的HER 2阳性CTC不太可能反映肿瘤的活性，并可能预测曲妥珠单抗的应答。
Purpose: Early metastasis in node-negative breast cancer indicates that breast cancer cells obviously can bypass the lymph nodes and disseminate directly hematogenous to distant organs. For this purpose, we evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months.Experimental Design: Cells were isolated by the patented combined buoyant density gradient and immunomagnetic separation procedure and analyzed by immunocytochemistry.Results: We detected one to eight CTCs in the peripheral blood of 17 of 35 patients (48.6%) presenting no overt metastasis. As a positive control, 7 of 7 (100%) patients with metastatic disease presented positive. Healthy persons and patients (n = 32) operated for nonmalignant diseases presented negative for CTCs. The presence and frequency of HER2-positive CTCs correlated with a significantly decreased disease-free survival (P < 0.005) and overall survival (P < 0.05). Interestingly, in 12 patients with HER2-positive CTCs, the primary tumor was negative for HER2 as assessed by immunohistochemical score and fluorescence in situ hybridization.Conclusions: This study provides some evidence of a prognostic effect of HER2-positive CTCs in stage I to III breast cancer. Future studies have to determine the outcome of patients treated with HER2-targeting therapies with respect to HER2-positive CTC levels because it is not unlikely that high levels of HER2-positive CTCs reflect the activity of the tumor and may predict response to trastuzumab.