High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).
High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).
复制标题
DOI：
10.1158/1078-0432.ccr-17-1864
复制
发表时间：
2018-07-01
期刊：
影响因子：
--
通讯作者：
Perez EA
中科院分区：
文献类型：
--
作者：
Chumsri S;Sperinde J;Liu H;Gligorov J;Spano JP;Antoine M;Moreno Aspitia A;Tan W;Winslow J;Petropoulos CJ;Chenna A;Bates M;Weidler JM;Huang W;Dueck A;Perez EA
p95HER2是人表皮生长因子受体2 （HER2）的截断形式，在体外对曲妥珠单抗具有耐药性，但迄今为止临床结果相互矛盾。鉴于p95HER2水平与HER2总表达水平相关，从而获得更好的结果，我们试图评估中北部癌症治疗组N0337和N98-32-52试验中p95HER2/HER2比率。使用HERmark法和VeraTag技术（Monogram Biosciences）测量91例患者样本中HER2和p95HER2的总表达水平。在多变量模型中，总HER2水平升高与总生存期（OS）延长显著相关（风险比[HR]=0.33； P= 0.002）， p95HER2水平降低与总生存期（OS）延长显著相关（风险比[HR]= 4.2； P= 0.01）。总HER2表达水平与更长的无进展生存期（PFS）显著相关（HR=0.57； P= 0.04），而p95HER2表达水平与更长的无进展生存期（PFS）无关（HR= 1.7； P= 0.25）。然而，p95HER2与HER2总表达水平呈正相关（R2= 0.48； P< 0.001）。与我们的假设一致，p95HER2/HER2的比值与PFS （HR= 1.7； P= 0.04）和OS （HR=2.8； P= 0.002）恶化显著相关。p95HER2/HER2值最高的患者的PFS （HR=1.8， P= 0.06）和OS （HR=2.3， P= 0.02）较差。高p95HER2/HER2比值确定了转移性乳腺癌患者，基于曲妥珠单抗的治疗结果较差。p95HER2/HER2比值可能为鉴别曲妥珠单抗预后不良的患者提供更好的生物标志物。p95HER2/HER2比值作为HER2靶向治疗的潜在预后或预测性生物标志物的进一步研究是有必要的。
p95HER2 is a truncated form of human epidermal growth factor receptor 2 (HER2) that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98–32-52 trials. The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples. In the multivariate model, increasing total HER2 level was significantly associated with longer overall survival (OS) (hazard ratio [HR]=0.33; P=.002) and decreasing p95HER2 level was significantly associated with longer OS (HR=4.2; P=.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR=0.57; P=.04) whereas p95HER2 level was not (HR= 1.7; P= .25). However, there was a positive association between p95HER2 and total HER2 expression levels (R2= 0.48; P<.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR= 1.7; P= .04) and OS (HR=2.8; P=.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR=1.8; P=.06) and OS (HR=2.3; P=.02). A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. p95HER2/HER2 ratio may provide better biomarker to identify patients with poor outcome on trastuzumab. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted.