Sekine Ikuo, Shimizu Chikako, Nishio Kazuto, Saijo Nagahiro, Tamura Tomohide
Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
Int J Clin Oncol. 2009 Apr;14(2):112-9. doi: 10.1007/s10147-008-0813-z. Epub 2009 Apr 24.
We aimed to identify, through a review of the literature, candidate genes for a prospective predictive chemosensitivity test in patients with breast cancer.
Papers demonstrating an association between gene alterations in tumor tissue and clinical chemosensitivity in breast cancer patients were selected by Medline searches. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) of response rates for patients who had tumors with or without gene alteration. Combined ORs and CIs were estimated using the DerSimonian-Laird method.
A total of 18 genes were evaluated for association with clinical chemosensitivity in 6378 patients registered in 69 studies. The median (range) number of patients in each study was 73 (29-319). Overexpression of ABCB1 (P-glycoprotein) was associated with poor responses to first-line chemotherapy (combined OR [CI], 0.16 [0.05-0.59]; n = 322). Overexpression and amplification of TOP2A (topoisomerase II-alfa) were more frequently observed in patients who responded to first-line chemotherapy (combined OR [CI], 2.73 [1.02-7.27]; n = 323). Overexpression of ERBB2 (c-erbB2) was associated with favorable responses in patients treated with both first-line anthracycline-based chemotherapy and second-line taxane-based chemotherapy (combined ORs [CIs], 1.60 [1.19-2.17]; n = 1807 and 2.24 [1.06-4.74]; n = 259, respectively). BCL2 overexpression was associated with resistance to first-line chemotherapy (combined OR [CI], 0.44 [0.21-0.91]; n = 816).
ABCB1, TOP2A, ERBB2, and BCL2 were good candidates for future clinical trials of predictive chemosensitivity tests in patients with breast cancer.
我们旨在通过文献回顾，确定可用于乳腺癌患者前瞻性预测化疗敏感性试验的候选基因。
通过检索Medline选择那些证明肿瘤组织基因改变与乳腺癌患者临床化疗敏感性之间存在关联的论文。我们计算了肿瘤有或无基因改变患者的反应率的比值比（OR）及其95%置信区间（CI）。使用DerSimonian-Laird方法估计合并的OR和CI。
在69项研究中登记的6378例患者中，共评估了18个基因与临床化疗敏感性的关联。每项研究中的患者中位数（范围）为73例（29 - 319例）。ABCB1（P-糖蛋白）过表达与一线化疗反应不佳相关（合并OR [CI]，0.16 [0.05 - 0.59]；n = 322）。TOP2A（拓扑异构酶II-α）过表达和扩增在一线化疗有反应的患者中更常见（合并OR [CI]，2.73 [1.02 - 7.27]；n = 323）。ERBB2（c-erbB2）过表达与接受一线蒽环类化疗和二线紫杉类化疗的患者的良好反应相关（合并ORs [CIs]，分别为1.60 [1.19 - 2.17]；n = 1807和2.24 [1.06 - 4.74]；n = 259）。BCL2过表达与一线化疗耐药相关（合并OR [CI]，0.44 [0.21 - 0.91]；n = 816）。
ABCB1、TOP2A、ERBB2和BCL2是未来乳腺癌患者预测化疗敏感性试验临床试验的良好候选基因。
