ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy

Abstract

Expression of the adenosine triphosphate-binding cassette B1 (ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.

Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan

“…Synonymous SNPs as C3435T and C1236T decrease the levels of mRNA expression and, hence, overall P-gp activity (Pongstaporn et al, 2015), whereas, G 2677A/T leads to change of alanine amino acid with serine or threonine. Many studies discussed the relation between the three SNPs and the incidence of breast cancer (Ji et al, 2012;Tulsyan et al, 2014;Gutierrez-Rubio et al, 2015;Kim et al, 2015). However, the findings of these studies are still inconclusive (Wang et al, 2013a;Gutierrez-Rubio et al, 2015).…”

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients

“…However, inter-patient variability has created a major obstacle for the clinical use of anticancer drugs [8]. Studies showed that these variations may be caused by differences in metabolizing enzymes and transporters associated with DOX.…”

A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network

“…TOP1 and TOP2A were reported to inhibit the breast cancer resistant proteins [40]. ABCB1 is known as prognostic factor in breast cancer patients [41]. CASP3 expression loss represents an important cell survival mechanism in breast cancer patients [42] and it inhibits the growth of breast cancer cells.…”