Exploratory analysis of candidate germline gene polymorphisms in breast cancer patients treated with neoadjuvant anthracycline-containing chemotherapy and associations with febrile neutropenia

Pharmacogenomics. 2015;16(11):1267-76. doi: 10.2217/PGS.15.74. Epub 2015 Aug 20.

Abstract

Aim: SNPs may be associated with (side) effects of chemotherapy and may be useful as biomarkers to predict febrile neutropenia.

Patients & methods: 187 DNA samples extracted from formalin-fixed paraffin-embedded tissue from patients with stage II/III HER2-negative breast cancer were genotyped.

Results: Candidate SNPs were selected and explored for association with febrile neutropenia and/or pathological complete response. TT genotype of 388 C>T in FGFR4 (rs351855) had a tendency toward higher incidence of febrile neutropenia during neoadjuvant chemotherapy, compared with the CT (p = 0.383) genotype and compared with the CC genotype (p = 0.068).

Conclusion: The TT genotype of 388 C>T FGFR4 may be related to incidence of febrile neutropenia during neoadjuvant TAC (docetaxel, doxorubicin, cyclophosphamide) chemotherapy and is possibly useful as a patient-related risk factor when assessing febrile neutropenia risk. Original submitted 23 January 2015; Revision submitted 26 May 2015.

Keywords: SNPs; breast cancer; febrile neutropenia; neoadjuvant; pCR; polymorphisms.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / adverse effects*
  • Anthracyclines / therapeutic use*
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Febrile Neutropenia / chemically induced*
  • Febrile Neutropenia / epidemiology
  • Febrile Neutropenia / genetics*
  • Female
  • Genotype
  • Germ-Line Mutation / genetics*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic