title: 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.
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Ham
authors.forename: Kyung Hun
authors.initials: KH
authors.lastname: Lee
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D043823:Taxoids / Q000008:administration & dosage
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A
keywords: ABCB1 Gene; C3435T; breast cancer; neoadjuvant chemotherapy; single nucleotide polymorphism