Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel based chemotherapy in breast cancer patients

Background: The chemotherapy resistance and toxicity of chemotherapy are major problems in breast cancer treatment. However, candidate biomarkers for predicting clinical outcomes and better prognosis remain lacking. Methods: In this study, we analyzed possible impact of 8 genetic variants of fibroblast growth factor receptor1-4 (FGFR1-4) on the treatment response and toxicities in 211 breast cancer patients. DNA was extracted from peripheral blood cells, and the genotypes were examined using the TaqMan Pre-Designed SNP Genotyping Assays. Results: The FGFR4 rs1966265 and FGFR2 rs2981578 contributed to clinical outcome of breast cancer treated with docetaxel-epirubicin-cyclophosphamide (CET)-based chemotherapy. For rs1966265, AA genotype had significant correlation with the clinical response to neoadjuvant chemotherapy (NCT) when compared with GG and AG/GG genotype (P = 0.019 and P = 0.004, respectively). Moreover, A allele of FGFR2 rs2981578 had significant rates of response (P = 0.025). In addition, rs2420946 CC genotype was associated with higher frequency of toxicities compared with II and CT/II genotypes (P= 0.038 and P= 0.019, respectively). Also, rs2981578 AG genotype showed higher frequency of toxicities compared with GG genotype (P < 0.0001). Conclusions: The results suggest these polymorphisms, especially rs1966265 and rs2981578, might be candidate pharmacogenomics factors to the response and prognosis prediction for individualized CET-based chemotherapy in breast cancer patients.