Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients
Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients
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DOI：
10.1093/annonc/mdn624
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发表时间：
2009-02-01
影响因子：
50.5
通讯作者：
Chung, H. C.
中科院分区：
文献类型：
--
作者：
Chang, H.;Rha, S. Y.;Chung, H. C.
背景：ABCB 1是多药耐药的主要机制，许多癌症发展耐药性化疗药物。ABCB 1基因多态性是否与癌症患者化疗后的生存率和疗效相关仍存在争议。我们评估了ABCB 1基因多态性2677 G> T/A或3435 C> T的转移性乳腺癌患者接受紫杉醇单药治疗的临床结局（安全性和有效性）之间的相关性。患者和方法：转移性乳腺癌患者接受175 mg/m2紫杉醇治疗，每3周为1周期。使用来自患者的外周血单个核细胞对ABCB 1 2677 G> T/A和3435 C> T多态性进行基因分型。基因型与肿瘤反应，生存，毒性和耐药性进行了调查，结果：ABCB 1 3435 CT表现出明显低于CC基因型的疾病控制率（P = 0.025）。在考克斯回归分析中，ABCB 1 3435 CT与较短的总生存期（OS）相关（P = 0.026）。2677 GG基因型与紫杉醇和蒽环类药物的耐药性显著相关（P分别为0.04和0.04）。结论：ABCB 1基因型可能是紫杉醇活性的预测因子，也是转移性乳腺癌患者的预后因素。
Background: ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G > T/A or 3435C > T.Patients and methods: Patients with metastatic breast cancer were treated with 175 mg/m(2) paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G > T/A and 3435C > T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance.Results: ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity.Conclusions: ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patients.