Chen Jiarong, Yang Canhong, Guo Bin, Sena Emily S, Macleod Malcolm R, Yuan Yawei, Hirst Theodore C
Department of Oncology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong 529030, P. R. China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou DaDao Bei, Guangzhou, Guangdong 510515, P. R. China.
PLoS One. 2016 Jul 27;11(7):e0158240. doi: 10.1371/journal.pone.0158240. eCollection 2016.
Breast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer.
We searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias.
We included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%). Median survival was prolonged by a factor of 1.45 (1.30-1.62). Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias.
We have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.
乳腺癌是最常见的癌症，是女性癌症死亡的第二大主要原因。曲妥珠单抗是一种有效的治疗方法，是第一种针对人表皮生长因子受体2（HER2）的单克隆抗体。为了为其他有效治疗方法的开发提供信息，我们报告了曲妥珠单抗在乳腺癌动物模型中对生存和肿瘤体积疗效的汇总估计。
我们系统检索了PubMed和EMBASE，以识别在乳腺癌动物模型中测试曲妥珠单抗的出版物。提取了描述肿瘤体积、中位生存期和动物特征的数据，并使用12项清单评估质量。我们分析了研究设计和质量的影响以及发表偏倚的证据。
我们纳入了83项研究的数据，报告了169项实验，使用了2076只小鼠。曲妥珠单抗治疗使肿瘤生长大幅减少，治疗动物的肿瘤生长至对照动物肿瘤体积的32.6%（95%CI 27.8%-38.2%）。中位生存期延长了1.45倍（1.30-1.62）。许多研究设计和质量特征导致了研究间的异质性，我们发现了表明发表偏倚的证据。
我们发现在一系列实验情况下，曲妥珠单抗在动物乳腺癌模型中是有效的。然而，发表偏倚的存在以及减少偏倚措施的低普及率为未来临床前乳腺癌研究的改进提供了重点。
