Background: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy. Objectives: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel. Methods: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin. Results: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). Conclusion: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.
Background: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. Objectives: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). Methods: We determined the genotypes of CYP3A5(*3), MDR1 (2677G→T at exon 21 and 3435C→T at exon 26 and their haplotypes) and COX-2 (–1195G→A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The χ2 test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. Results: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (–1195G) is likely to result in a better response to vinorelbine (nonsignificant). Conclusions: Our findings suggest that MDR1 2677G→T/A and 3435C→T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.
Aim: The purposes of our study were to compare the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) patients with or without trastuzumab treatment and HER2-negative patients, and to explore factors that might predict the survival benefit associated with trastuzumab treatment in HER2-positive breast cancer. Patients and Methods: A total of 421 patients with mBC were analyzed in this retrospective study. All patients had first-line chemotherapy with or without trastuzumab. They were classified into 3 groups according to their HER2 status and trastuzumab treatment: HER2-positive mBC patients with or without trastuzumab treatment and HER2-negative patents. Results: Trastuzumab administration in HER2-positive mBC patients significantly prolonged overall survival (33 vs. 26 months; P = 0.003) and led to a 49.8% reduction in death risk. In the subgroup analysis, HER2-positive patients with hormone receptor (HR)-negative status (29 vs. 17 months; P = 0.000) or visceral metastasis (30 vs. 21 months; P = 0.000) had more survival benefit when treated with trastuzumab. Conclusions: Trastuzumab administration significantly improved the overall survival in HER2-positive mBC patients, who gained a prognosis comparable to that of patients with HER2-negative disease. HR status and metastasis site might be important surrogate makers that predict survival benefit from trastuzumab-based treatment.
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