Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
Translational Oncology Unit, Albacete University Hospital, Albacete, Spain.
Cancer Treat Rev. 2014 Oct;40(9):1048-55. doi: 10.1016/j.ctrv.2014.08.003. Epub 2014 Sep 3.
Receptor tyrosine kinases (RTKs) may facilitate tumor progression if activated aberrantly. The prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression and effectiveness of its therapeutic targeting is well established, but the effects on prognosis of overexpression of other RTKs is unknown. Here we evaluate the association of RTK expression and survival in breast cancer.
PubMed was searched to identify studies evaluating the association between expression of RTKs other than HER2 and survival of women with breast cancer. Published data were extracted and computed into odds ratios (OR) for death at 5 years with 95% confidence intervals (CI). Data were pooled in a meta-analysis using the Mantel-Haenszel random-effect model. For studies reporting data for more than one RTK the lowest and highest OR were used for separate analyses.
Sixteen studies comprising 11,056 patients were included in the analysis. There was an association between overexpression of RTKs and decreased 5-year OS and this was highly significant when using highest ORs from studies reporting more than one RTK (OR=2.42; 95% CI=1.92-3.06, P<0.001). Similar results were observed for 5-year BCSS. Worse OS was seen with overexpression of fibroblast growth factor receptor 2/3 (FGFR) (OR=3.81; 95% CI=1.79-8.11) and epidermal growth factor receptor (EGFR)/HER1 (OR=2.45; 95% CI=1.90-3.15).
Overexpression of various RTKs is associated with poor outcomes. This data suggests the clinical evaluation of combination of agents against RTKs or relevant oncogenic nodes.
如果受体酪氨酸激酶 (RTKs) 异常激活，可能会促进肿瘤进展。人表皮生长因子受体 2 (HER2) 过表达的预后影响及其治疗靶向的有效性已得到充分证实，但其他 RTKs 过表达对预后的影响尚不清楚。在这里，我们评估了 RTK 表达与乳腺癌患者生存的关系。
通过 PubMed 搜索评估除 HER2 以外的 RTK 表达与女性乳腺癌患者生存之间关系的研究。提取已发表的数据，并计算为 5 年死亡的优势比 (OR) 及其 95%置信区间 (CI)。使用 Mantel-Haenszel 随机效应模型对数据进行荟萃分析。对于报告了多种 RTK 数据的研究，使用最低和最高 OR 进行单独分析。
共纳入了 16 项研究，包含 11056 例患者。RTK 过表达与 5 年 OS 降低有关，当使用报告了多种 RTK 的研究中的最高 OR 时，这种相关性具有高度显著性（OR=2.42；95%CI=1.92-3.06，P<0.001）。类似的结果也见于 5 年 BCSS。FGFR2/3（OR=3.81；95%CI=1.79-8.11）和表皮生长因子受体 (EGFR)/HER1（OR=2.45；95%CI=1.90-3.15）过表达与 OS 更差相关。
各种 RTK 的过表达与不良结局相关。这些数据表明，需要对针对 RTKs 或相关致癌节点的联合药物进行临床评估。
