Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
Breast Cancer Res Treat. 2011 Feb;126(1):109-17. doi: 10.1007/s10549-010-1316-y. Epub 2010 Dec 29.
Human epidermal growth factor receptor 2 (HER2) testing is an essential part of pathological assessment in breast cancer patients, as HER2 provides not only prognostic but also predictive information on response to targeted therapy. So far, HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques is still under debate, and more reliable and robust technologies are needed. To address this issue and to evaluate the predictive value of HER2 on chemotherapy, we investigated a cohort of 278 patients from the GeparTrio trial, a prospective neoadjuvant anthracycline/taxane-based multicenter study. In the GeparTrio trial, patients were not treated with any anti-HER2 therapy, as this was not standard therapy at this time. The HER2 status was analyzed by three different approaches: local and central evaluation using immunohistochemistry combined with in situ-hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR from formalin-fixed, paraffin-embedded (FFPE) tissue samples using a predefined cutoff. HER2 overexpression/amplification was observed in 37.3% (91/244) and 17.9% (41/229) of the informative samples in the local and central evaluations, respectively. Positive HER2 mRNA levels were found in 19.8% (55/278). We observed a highly significant correlation between central HER2 expression and HER2 status measured by kinetic RT-PCR (r = 0.856, P < 0.0001) and an overall agreement of 95.6% (κ statistic, 0.862, CI 0.77-0.94). Further, central HER2 as well as HER2 mRNA expression were predictors for a pathological complete response after neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate binary logistic regression analysis (OR 3.29, P = 0.002; OR 2.65, P = 0.004). The predictive value could be confirmed for the central HER2 status by multivariate analysis (OR 3.04, P = 0.027). The locally assessed HER2 status was not predictive of response to chemotherapy. Our results suggest that standardized methods are preferable for evaluation of HER2 status. The kinetic RT-PCR from FFPE tissue might be an additional approach for assessment of this important prognostic and predictive parameter but has to be confirmed by other studies.
人表皮生长因子受体 2（HER2）检测是乳腺癌患者病理评估的重要组成部分，因为 HER2 不仅提供预后信息，还提供对靶向治疗反应的预测信息。到目前为止，免疫组织化学/原位杂交技术的 HER2 检测准确性仍存在争议，需要更可靠和强大的技术。为了解决这个问题，并评估 HER2 对化疗的预测价值，我们对来自 GeparTrio 试验的 278 名患者进行了研究，这是一项前瞻性的新辅助蒽环类药物/紫杉烷类药物为基础的多中心研究。在 GeparTrio 试验中，患者未接受任何抗 HER2 治疗，因为这在当时不是标准治疗。HER2 状态通过三种不同的方法进行分析：使用免疫组织化学结合原位杂交的局部和中心评估，以及使用来自福尔马林固定、石蜡包埋（FFPE）组织样本的动力学 RT-PCR 评估 HER2 mRNA 表达，使用预设的截止值。在局部和中心评估中，分别有 37.3%（91/244）和 17.9%（41/229）的信息样本中观察到 HER2 过表达/扩增。在 278 名患者中，有 19.8%（55/278）发现 HER2 mRNA 水平呈阳性。我们观察到中心 HER2 表达与动力学 RT-PCR 测量的 HER2 状态之间存在高度显著的相关性（r=0.856，P<0.0001），总一致性为 95.6%（κ 统计量，0.862，CI 0.77-0.94）。此外，在单因素二项逻辑回归分析中，中心 HER2 以及 HER2 mRNA 表达是新辅助蒽环类药物/紫杉烷类药物为基础的原发性化疗后病理完全缓解的预测因子（OR 3.29，P=0.002；OR 2.65，P=0.004）。通过多因素分析可以证实中心 HER2 状态的预测价值（OR 3.04，P=0.027）。局部评估的 HER2 状态不能预测对化疗的反应。我们的结果表明，标准化方法更适合评估 HER2 状态。来自 FFPE 组织的动力学 RT-PCR 可能是评估这一重要预后和预测参数的另一种方法，但需要其他研究加以证实。
