HER-3 Overexpression Is Prognostic of Reduced Breast Cancer Survival A Study of 4046 Patients
HER-3 Overexpression Is Prognostic of Reduced Breast Cancer Survival A Study of 4046 Patients
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DOI：
10.1097/sla.0b013e3181dbb77e
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发表时间：
2010-06-01
影响因子：
9
通讯作者：
Wiseman, Sam M.
中科院分区：
文献类型：
--
作者：
Chiu, Connie G.;Masoudi, Hamid;Wiseman, Sam M.
简介：分子生物学的进展已经导致鉴定出在人类癌症中具有预后和治疗重要性的潜在标志物。HER-2检测和靶向治疗现在是乳腺癌管理的关键基石。本研究的目的是确定HER-3过度表达和HER-4过度表达的侵袭性breast cancer.Methods的频率和预后意义：组织微阵列使用临床注释福尔马林固定和石蜡包埋的肿瘤样本从4046例诊断为浸润性乳腺癌，平均随访12.5年。1型生长因子受体家族成员HER-1，HER-2，HER-3和HER-4表达水平通过免疫组织化学测定，HER-2状态通过荧光原位杂交进一步解析。结果：HER-3过表达在10.0%的肿瘤中被鉴定，在单变量分析中，HER-3过表达是乳腺癌患者特异性生存率降低的显著标志（P = 1.32 × 10 - 5）。此外，在HER-1和HER-2表达水平正常的肿瘤中，HER-3的过表达对疾病特异性生存具有显著的负面预后影响（HR：1.541，95% CI：1.166-2.036，P = 2.37 x 10（-3））独立于患者诊断时的年龄、雌激素受体状态、肿瘤分级、肿瘤大小、淋巴结状态，以及存在癌症的淋巴或血管侵入。HER-4过表达在78.2%的乳腺癌中被确定，并且不是患者生存的显著标志物（P = 0.214）。所有统计检验的结果均在验证数据集analysis.Conclusions：HER-3状态是浸润性乳腺癌患者疾病特异性生存的重要预后标志。因此，HER-3表达水平的评估可以鉴定具有不良疾病预后的患者亚组，并且可以对HER-3靶向抗癌剂的功效进行进一步评估。
Introduction: Advances in molecular biology have led to the identification of potential markers of prognostic and therapeutic importance in human cancers. HER-2 testing and targeted therapy now represents a critical cornerstone in the management of breast cancer. The objectives of the current study were to determine the frequency and prognostic significance of HER-3 over-expression and HER-4 over-expression by invasive breast cancer.Methods: Tissue microarrays were constructed using clinically annotated formalin-fixed and paraffin-embedded tumor samples from 4046 patients diagnosed with invasive breast carcinoma with a median 12.5 years of follow-up. Type 1 growth factor receptor family members HER-1, HER-2, HER-3, and HER-4 expression levels were determined by immunohistochemistry, and HER-2 status was further resolved by fluorescent in-situ hybridization. The study cohort was randomly divided and analyzed as a core data set and a validation data set.Results: HER-3 over-expression was identified in 10.0% of tumors and was a significant marker of reduced patient breast cancer-specific survival on univariate analysis (P = 1.32 x 10(-5)). Furthermore, in tumors with normal expression levels of HER-1 and HER-2, the overexpression of HER-3 had a significant negative prognostic effect on disease-specific survival (HR: 1.541, 95% CI: 1.166-2.036, P = 2.37 x 10(-3)) independent of patient age at diagnosis, Estrogen receptor status, tumor grade, tumor size, nodal status, and the presence of lymphatic or vascular invasion by cancer. HER-4 overexpression was identified in 78.2% of breast cancers and was not a significant marker of patient survival (P = 0.214). Results of all statistical tests were positively confirmed in the validation data set analysis.Conclusions: HER-3 status is an important prognostic marker of disease-specific survival in patients with invasive breast cancer. Accordingly, evaluation of the HER-3 expression level may identify a subset of patients with a poor disease prognosis, and who could undergo further evaluation for the efficacy of HER-3 targeted anticancer agents.