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PKP-004 Adverse events associated with Single Nucleotide Polymorphisms in breast cancer patients treated with docetaxel-based chemotherapy
  1. A García Robles1,
  2. V Bosó Ribelles1,
  3. M Cueto Sola1,
  4. J Ruiz Ramos1,
  5. MJ Company Albir1,
  6. MJ Herrero Cervera1,
  7. SF Aliño Pellicer2,
  8. JL Poveda Andrés1
  1. 1Hospital Universitari i Politècnic La Fe, Pharmacy, Valencia, Spain
  2. 2University of Valencia, Pharmacology, Valencia, Spain

Abstract

Background Inter-individual differences in drug response are linked, in many cases, to single nucleotide polymorphisms (SNPs) in genes coding for drug-metabolising enzymes and transporters. Docetaxel is active for several tumour types, including breast cancer, but its use is limited by toxicity.

Purpose To evaluate the associations between a panel of 86 SNPs in 32 genes and toxicities developed by breast cancer patients treated with docetaxel.

Materials and methods Between June 2011 and February 2013 breast cancer patients treated with docetaxel plus cyclophosphamide ± doxorubicin who gave informed consent were genotyped. Genomic DNA was analysed by a genetic analysis platform (MassArray, Sequenom). The Hardy-Weinberg equilibrium was assessed. The association between genotypes and toxicities was assessed with Fisher’s exact test.

Results Thirty-nine Caucasian women (median age: 48.2 years old; range: 33.7–75.8) were genotyped. Genotype frequencies were in Hardy-Weinberg equilibrium. 79.5% (n = 31) of the patients were treated with docetaxel plus cyclophosphamide and doxorubicin and 20.5% (n = 8) with docetaxel plus cyclophosphamide. Significant associations between SNP genotypes and toxicities are shown in the table. No associations with neurotoxicity were found.

View this table:
Abstract PKP-004 Table 1

Conclusions Genetic variations in ABCB1, NOS3 and ERCC1 have been related to incidences of anaemia, neutropenia, diarrhoea and mucositis in docetaxel-treated breast cancer patients. These results need to be validated in a bigger population in order to be translated into clinical practice.

No conflict of interest.

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