Analysis of plasma HER2 copy number in cell-free DNA of breast cancer patients: a comparison with HER2 extracellular domain protein level in serum
Analysis of plasma HER2 copy number in cell-free DNA of breast cancer patients: a comparison with HER2 extracellular domain protein level in serum
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DOI：
10.1007/s12282-020-01212-x
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发表时间：
2021-02-04
期刊：
影响因子：
4
通讯作者：
Iwase, Hirotaka
中科院分区：
文献类型：
--
作者：
Qui, Shi;Takeshita, Takashi;Iwase, Hirotaka
背景HER 2（人表皮生长因子受体2）状态已在乳腺癌（BC）组织中通过免疫组化或原位杂交进行了评估。我们评估了来自血液样品的血浆无细胞DNA（cfDNA）中的HER 2拷贝数（CN）测定，并将其与血清中HER 2胞外结构域（ECD）的蛋白质测量进行比较。方法应用抗HER 2单克隆抗体，采用化学发光免疫分析法测定血清HER 2-ECD水平。对120例原发性乳腺癌、30例转移性乳腺癌和34例新辅助化疗患者的临床资料进行分析。本研究由熊本大学医学研究审查进展第1857号批准。结果在原发性和转移性HER 2阳性乳腺癌中，HER 2-CN比值与HER 2-ECD水平呈正相关（分别为P = 0.003和P < 0.001）。HER 2-ECD水平在转移部位较多的患者中显著较高（P = 0.02）。通过ROC曲线分析评价的HER 2水平在区分原发性和转移性HER 2阳性BC中的有用性在HER 2-ECD测定中比在HER 2-CN测定中更好。34例接受NAC治疗的患者中，治疗前后HER 2-CN比值略有下降（P = 0.10），而HER 2-ECD水平明显下降（P < 0.001）。结论与HER 2-ECD水平相比，HER 2-CN比值的临床应用价值稍逊。需要改进测量方法并进一步检查与长期预后的相关性以及通过HER 2-CN和HER 2-ECD测定分析对抗HER 2治疗的应答。
Background HER2 (human epidermal growth factor receptor 2) status has been evaluated in breast cancer (BC) tissues by immunohistochemistry or in situ hybridization. We evaluated HER2 copy number (CN) assay in plasma cell-free DNA (cfDNA) from blood samples and compared it with protein measurements of HER2 extracellular domain (ECD) in serum. Methods Serum HER2-ECD levels were measured by chemi-luminescence immunoassay using anti-HER2 monoclonal antibodies. Analyses were performed on 120 cases of primary BC, 30 cases of metastatic BC and 34 cases treated by neoadjuvant chemotherapy (NAC). This study was approved by Medical Research Review Advancement No. 1857 for Kumamoto University. Results There was a positive correlation between HER2-CN ratios and HER2-ECD levels, in primary (n = 54) and metastatic (n = 30) HER2-positive BC (P = 0.003 and P < 0.001, respectively). HER2-ECD levels were significantly higher in patients with a larger number of metastatic sites (P = 0.02). The usefulness of HER2 levels in discriminating primary and metastatic HER2-positive BC evaluated by ROC curve analysis was better in the HER2-ECD assay than in the HER2-CN assay. In 34 patients who received NAC, there was a small decrease in HER2-CN ratios between before and after NAC (P = 0.10), while there was an obvious decrease in HER2-ECD levels between before and after NAC (P < 0.001). Conclusion Compared to HER2-ECD levels, the clinical usefulness of HER2-CN ratio was somewhat inferior. Improved measurement methods and further examination of the association with long-term prognosis and the response to anti-HER2 treatment analyzed by HER2-CN and HER2-ECD assay are required.