ABSTRACT
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can lead to a significant deterioration in the quality of life of cancer patients receiving chemotherapy. This study aimed to determine whether ABCB1 2677G > T/A was associated with complete response (CR; defined as no vomiting and no rescue medication) in acute phase (CR0-24), as well as to explore the genetic factors affecting delayed phase (CR24-120) CINV in cancer patients treated with a standard triple antiemetic regimen that included aprepitant. METHODS: This prospective single-center study included a total of 166 chemotherapy-naïve patients with breast cancer who received a standard dose of doxorubicin and cyclophosphamide combination chemotherapy; granisetron, dexamethasone, and aprepitant were administered prior to chemotherapy. CR0-24 was compared between minor allele homozygous (TT, AA, and TA) and major allele homozygous plus heterozygous (GG, GA, and GT) groups of ABCB1 2677G > T/A. In addition, 14 genetic polymorphisms were genotyped and their associations with CRs were investigated. RESULTS: The proportion of patients who achieved CR0-24, which was the primary endpoint of this study, was 59% in the minor allele homozygous and 61% in the major allele homozygous plus heterozygous groups of ABCB1 2677G > T/A. Although this difference was not statistically significant, multivariate logistic regression analysis adjusted for potential risk factors showed that TACR1 1323TT (OR, 2.57; P = 0.014) was a significant determinant of CR24-120. CONCLUSION: No significant association was found between ABCB1 2677G > T/A and CR0-24. However, it was observed that the polymorphism of TACR1, which encodes the neurokinin 1 receptor, might be a potential genetic risk factor for the development of delayed phase CINV.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Nausea/chemically induced , Receptors, Neurokinin-1/genetics , Vomiting/chemically induced , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Antiemetics/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Aprepitant/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Middle Aged , Nausea/drug therapy , Nausea/genetics , Pharmacogenetics , Prospective Studies , Quality of Life , Vomiting/drug therapy , Vomiting/geneticsABSTRACT
Chemotherapy-induced neutropenia is one of the major adverse events which results in the reduction of chemotherapy. Doxorubicin is a substrate of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter; reportedly, ABCB1 polymorphisms influence doxorubicin pharmacokinetics. We evaluated the association between chemotherapy-induced neutropenia and ABCB1 polymorphisms in patients with breast cancer. We investigated 141 patients with breast cancer treated with doxorubicin and cyclophosphamide (AC) chemotherapy. Peripheral blood samples obtained from patients were genotyped for the ABCB1 2677G>T/A and 3435C>T polymorphisms. The genotypes were then investigated for their association with grade 3 or greater neutropenia, and further their risk factors were examined using a multivariate logistic regression. The proportion of patients with grade 3 or greater neutropenia was 85.7% in the homozygous variant group, and 80% and 58.6% in the heterozygous variant and GG genotype groups, respectively (p = 0.021). The multivariate logistic regression analysis revealed that the ABCB1 2677G>T/A polymorphism was a strong predictor of grade 3 or greater neutropenia (odds ratio: 3.76; 95% confidence interval: 1.44-9.81; p = 0.007). ABCB1 polymorphisms may influence the extent of chemotherapy-induced neutropenia in AC combination-treated patients with breast cancer.
