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

BMC Cancer. 2018 Oct 25;18(1):1038. doi: 10.1186/s12885-018-4951-z.

Abstract

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 TT and CT/TT 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.

Keywords: Breast cancer; Fibroblast growth factor receptors; Neoadjuvant chemotherapy; Single-nucleotide polymorphism; rs1966265; rs2981578.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cyclophosphamide / administration & dosage
  • Docetaxel / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Receptors, Fibroblast Growth Factor / genetics*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Treatment Outcome

Substances

  • Receptors, Fibroblast Growth Factor
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide