An update on biomarkers of potential benefit with bevacizumab for breast cancer treatment: Do we make progress?

As the first monoclonal antibody against vascular endothelial growth factor(VEGF), bevacizumab(BEV) is a definitely controversial antiangiogenic therapy in breast cancer. The initial excitement over improvements in progression-free survival(PFS) with BEV was tempered by an absence of overall survival(OS) benefit and serious adverse effects. Missing targeted population urged us to identify the predictive biomarkers for BEV efficacy. In this review we focus on the research in breast cancer and provide recent investigations on clinical, radiological,molecular and gene profiling markers of BEV efficacy, including the new results from randomized phase III clinical trials evaluating the efficacy of BEV in combination with comprehensive biomarker analyses. Current evidences indicate some predictive values for genetic variants, molecular imaging, VEGF pathway factors or associated factors in peripheral blood and gene profiling. The current challenge is to validate those potential biomarkers and implement them into clinical practice.

Effect of ABCB1 3435C>T transporter gene polymorphism on plasma efavirenz concentration in HIV-1 infected Thai adults

Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=21)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was 0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=27)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Conclusions:There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB13435 T/T and ABCB13435 C/T genotypes.No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.