Authors' Affiliations: Military Institute of Medicine, Warsaw; Lublin Oncology Center, Lublin; Białystok Oncology Center, Białystok; Greater Poland Cancer Center, Poznań; West Pomeranian Oncology Center, Szczecin; Opole Oncology Center, Opole; Warmia and Masuria Oncology Center, Olsztyn; Bydgoszcz Oncology Center, Bydgoszcz; Beskidy Oncology Center, Bielsko-Biała; Medical University of Gdańsk, Gdańsk, Poland; and Monogram Biosciences, Inc., South San Francisco, California.
Authors' Affiliations: Military Institute of Medicine, Warsaw; Lublin Oncology Center, Lublin; Białystok Oncology Center, Białystok; Greater Poland Cancer Center, Poznań; West Pomeranian Oncology Center, Szczecin; Opole Oncology Center, Opole; Warmia and Masuria Oncology Center, Olsztyn; Bydgoszcz Oncology Center, Bydgoszcz; Beskidy Oncology Center, Bielsko-Biała; Medical University of Gdańsk, Gdańsk, Poland; and Monogram Biosciences, Inc., South San Francisco, California
Clin Cancer Res. 2014 May 15;20(10):2805-13. doi: 10.1158/1078-0432.CCR-13-2782. Epub 2014 Mar 25.
P95HER2 (p95) is a truncated form of the HER2, which lacks the trastuzumab-binding site and contains a hyperactive kinase domain. Previously, an optimal clinical cutoff of p95 expression for progression-free survival (PFS) and overall survival (OS) was defined using a quantitative VeraTag assay (Monogram Biosciences) in a training set of trastuzumab-treated metastatic breast cancer (MBC) patients.
In the current study, the predictive value of the p95 VeraTag assay cutoff established in the training set was retrospectively validated for PFS and OS in an independent series of 240 trastuzumab-treated MBC patients from multiple institutions.
In the subset of 190 tumors assessed as HER2-total (H2T)-positive using the quantitative HERmark assay (Monogram Biosciences), p95 VeraTag values above the predefined cutoff correlated with shorter PFS (HR = 1.43; P = 0.039) and shorter OS (HR = 1.94; P = 0.0055) where both outcomes were stratified by hormone receptor status and tumor grade. High p95 expression correlated with shorter PFS (HR = 2.41; P = 0.0003) and OS (HR = 2.57; P = 0.0025) in the hormone receptor-positive subgroup of patients (N = 78), but not in the hormone receptor-negative group. In contrast with the quantitative p95 VeraTag measurements, p95 immunohistochemical expression using the same antibody was not significantly correlated with outcomes.
The consistency in the p95 VeraTag cutoff across different cohorts of patients with MBC treated with trastuzumab justifies additional studies using blinded analyses in larger series of patients.
p95HER2（p95）是 HER2 的一种截断形式，缺乏曲妥珠单抗结合位点，包含一个高活性的激酶结构域。此前，在曲妥珠单抗治疗转移性乳腺癌（MBC）患者的训练集中，使用定量 VeraTag 检测（Monogram Biosciences）定义了 p95 表达的最佳临床截止值，用于无进展生存期（PFS）和总生存期（OS）。
在本研究中，回顾性验证了训练集中确定的 p95VeraTag 检测截止值在来自多个机构的 240 例接受曲妥珠单抗治疗的 MBC 患者的独立系列中的预测价值，用于 PFS 和 OS。
在使用定量 HERmark 检测（Monogram Biosciences）评估的 190 例 HER2-总（H2T）阳性肿瘤亚组中，超过预定义截止值的 p95VeraTag 值与较短的 PFS（HR = 1.43；P = 0.039）和较短的 OS（HR = 1.94；P = 0.0055）相关，这两个结果均按激素受体状态和肿瘤分级分层。在激素受体阳性患者亚组（N = 78）中，高 p95 表达与较短的 PFS（HR = 2.41；P = 0.0003）和 OS（HR = 2.57；P = 0.0025）相关，但在激素受体阴性组中则不然。与定量 p95VeraTag 测量相比，使用相同抗体的 p95 免疫组化表达与结果无显著相关性。
在接受曲妥珠单抗治疗的 MBC 患者的不同队列中，p95VeraTag 截止值的一致性证明了在更大系列患者中进行盲法分析的额外研究是合理的。
