曲妥珠单抗治疗后循环 HER2 DNA 可预测乳腺癌的生存和反应。
Circulating HER2 DNA after trastuzumab treatment predicts survival and response in breast cancer.
机构信息
Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, DK 8000 Aarhus C, Denmark.
出版信息
Anticancer Res. 2010 Jun;30(6):2463-8.
BACKGROUND
Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed.
PATIENTS AND METHODS
We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three weeks later (HER2 DNA (n=22), HER2 ECD (n=23)).
RESULTS
Pre-treatment levels of HER2 gene amplification and HER2 ECD did not correlate to clinical parameters. However, 9 out of 22 patients had a more than a 14% (2 x SD) reduction in HER2 gene amplification following treatment and showed improved response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data.
CONCLUSION
We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab.
背景
只有一部分乳腺癌患者对 HER2 抑制剂曲妥珠单抗有反应,因此需要寻找识别应答者的方法。
患者和方法
我们研究了 28 例经检测原发肿瘤中 HER2 基因扩增的转移性乳腺癌患者,这些患者接受了曲妥珠单抗联合化疗的治疗。在首次治疗前(n=28)和三周后第二次治疗前(HER2 DNA:n=22,HER2 ECD:n=23)采集血浆,检测循环 DNA 中 HER2 基因的扩增情况和 HER2 细胞外结构域(ECD)的含量。
结果
治疗前 HER2 基因扩增和 HER2 ECD 水平与临床参数均无相关性。然而,22 例患者中有 9 例治疗后 HER2 基因扩增降低超过 14%(2 x SD),表现出更好的应答(p=0.02)和总生存(p=0.05)。HER2 ECD 动力学与临床数据无相关性。
结论
我们认为血浆中 HER2 基因扩增的减少可预测对曲妥珠单抗更有利的反应。