Prospective randomized phase II study determines the clinical usefulness of genetic biomarkers for sensitivity to primary chemotherapy with paclitaxel in breast cancer
Prospective randomized phase II study determines the clinical usefulness of genetic biomarkers for sensitivity to primary chemotherapy with paclitaxel in breast cancer
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DOI：
10.1111/j.1349-7006.2010.01740.x
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发表时间：
2011-01
期刊：
影响因子：
5.7
通讯作者：
Yoshinori Ito;K. Nagasaki;Y. Miki;T. Iwase;F. Akiyama;M. Matsuura;R. Horii;M. Makita;N. Tokudome;M. Ushijima;M. Yoshimoto;S. Takahashi;T. Noda;K. Hatake
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文献类型：
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作者：
Yoshinori Ito;K. Nagasaki;Y. Miki;T. Iwase;F. Akiyama;M. Matsuura;R. Horii;M. Makita;N. Tokudome;M. Ushijima;M. Yoshimoto;S. Takahashi;T. Noda;K. Hatake
在乳腺癌患者中，紫杉烷和蒽环类药物在全身化疗中发挥着核心作用。通过评估病理反应，我们可以评估对主要化疗的敏感性。然而，预测紫杉烷反应的生物标志物尚未建立。我们进行了一项前瞻性随机试验，以评估根据肿瘤基因表达使用敏感性测试选择患者是否可以提高病理反应的可能性。五个基因被鉴定为源自显微切割乳腺肿瘤 DNA 基因谱微阵列的生物标志物。实验组（B1）术前在敏感性试验阳性时给予紫杉醇 12 个周期，每周一次 80 mg/m2，因此判断对紫杉醇敏感。当测试结果为阴性时，即对紫杉醇不敏感，则给予四个周期的 FEC100（B2 组）。在对照组 (A) 中，每周施用紫杉醇，但未使用敏感性测试。总共入组了 92 名患者并分析了 86 名患者。每组的病理缓解率 (pRR) 分别为 B1（预期对紫杉醇敏感）36.4%、A（对照）21.1%、B2 12.5%。通过敏感性测试选择每周接受紫杉醇治疗的患者并没有提高 pRR。该研究未能验证使用五种基因表达对乳腺癌患者进行紫杉醇初次化疗的敏感性测试。然而，这项研究表明，随机 II 期研究是获得生物标志物有用性的快速结论的有力工具，并且可以成为进一步大型临床试验的基础。 （《癌症科学》2011 年；102：130–136）
In patients with breast cancer, taxane as well as anthracycline play central roles in systemic chemotherapy. By evaluating the pathological response, we can gauge sensitivity to primary chemotherapy. However, biomarkers that would predict a response to taxane have not yet been established. We conducted a prospective randomized trial to evaluate whether selecting patients using sensitivity testing based on the gene expression of the tumor might enhance the probability of the pathological response. Five genes were identified as biomarkers derived from a microarray of DNA gene profiles from microdisected breast tumors. In the experimental arm (B1), 12 cycles of weekly paclitaxel, 80 mg/m2, were preoperatively given when the sensitivity test was positive and therefore judged to be sensitive to paclitaxel. When the test was negative, meaning insensitive to paclitaxel, four cycles of FEC100 were given (arm B2). In the control arm (A), paclitaxel was administered weekly without the use of the sensitivity test. A total of 92 patients were enrolled and 86 patients were analyzed. The pathological response rate (pRR) of each arm was 36.4% in B1 (expected sensitive to paclitaxel), 21.1% in A (control) and 12.5% in B2, respectively. Weekly paclitaxel‐treated patients selected by the sensitivity test did not enhance the pRR. The study failed to validate sensitivity testing using five gene expressions for primary chemotherapy with paclitaxel in patients with breast cancer. However, this study suggests that a randomized phase II study is a robust tool for obtaining a rapid conclusion on the usefulness of biomarkers and could be the foundation for further large clinical trials. (Cancer Sci 2011; 102: 130–136)