Background:
Epirubicin combined with
docetaxel is the cornerstone of
neoadjuvant chemotherapy (NAC) for
breast cancer. The efficacy of NAC for
luminal A
breast cancer patients is very limited, and single nucleotide polymorphism is one of the most important factors that influences the efficacy. Our study is aimed to explore
genetic markers for the efficacy of
epirubicin combined with
docetaxel for NAC in patients with
luminal A
breast cancer. Methods: A total of 421 patients with two stages of
luminal A
breast cancer were enrolled in this study from 2 centers. Among them 231 patients were included in the discovery cohort and 190 patients are in the replication cohort. All patients received
epirubicin 75 mg/m2 and
docetaxel 75 mg/m2 on day 1, in a 21-day cycle, a cycle for 2-6 cycles. Before treatment, 2 ml of peripheral blood was collected from each patient to isolate genomic
DNA. Fourteen functional variants potentially regulating
epirubicin/
docetaxel response genes were prioritized by CellMiner and bioinformatics approaches. Moreover,
biological assays were performed to determine the effect of genetic variations on response to
chemotherapy. Results: The patients carrying rs6484711 variant A allele suffered a poor response to
epirubicin and
docetaxel for NAC (OR = 0.37, 95% CI: 0.18-0.74, P = 0.005) in combined stage. Moreover, expression quantitative trait loci (eQTL) analyses and
luciferase reporter assays revealed that rs6484711 A allele significantly increased the expression of ABTB2. Subsequent
biological assays illustrated that upregulation of ABTB2 significantly reduced the apoptosis rate of
breast cancer cells and enhanced the chemo-resistance to
epirubicin. Conclusions: Our study demonstrated rs6484711 polymorphism regulating ABTB2 expression might predict efficacy to
epirubicin based NAC in
luminal A
breast cancer patients. These results provided valuable information about potential role of genetic variations in individualized
chemotherapy.