PHC-025 Single Nucleotide Polymorphisms Associated with Adverse Events in Taxane-Treated Breast Cancer Patients. (12th March 2013)

• Record Type: Journal Article
• Authors: Bosó-Ribelles, V; Herrero-Cervera, MJ; Santaballa-Beltran, A; Palomar-Abad, L; Cueva-Sapiña, H de la; Montalar-Salcedo, J; Aliño-Pellicer, SF; Poveda-Andrés, JL
• Is Part Of: European journal of hospital pharmacy. Volume 20(2013)Supplement 1
• Page Start: A134
• Page End: A134
• Publication Date: 2013-03-12
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2013-000276.370
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Background: Inter-individual differences in drug efficacy and toxicity are linked, in many cases, to single nucleotide polymorphisms (SNPs) in genes coding for drug metabolising enzymes and transporters. Taxanes are active for several tumour types, including breast cancer. But this is limited by adverse events such as neurotoxicity and haematological toxicity. Purpose: To evaluate the associations between a panel of 92 SNPs in 33 genes and adverse events developed by breast cancer patients treated with taxanes. Materials and Methods: Between June 2011 and May 2012 breast cancer patients treated with taxanes who gave informed consent were genotyped for 92 SNPs in 33 genes. Genomic DNA was analysed by a genetic analysis platform (MassArray, Sequenom). Hardy-Weinberg equilibrium was assessed. Clinical data were recorded. The association between genotypes and adverse reactions was assessed with Fisher's exact test and X2-test. Results: Sixty-seven Caucasian women (mean age: 53 years old; 95%CI = 49–56) were genotyped. All genotype frequencies were in Hardy-Weinberg equilibrium. 53.7% (n = 36) of the patients were treated with docetaxel and 46.3% (n = 31) with paclitaxel. Histotypes: 88.1% (n = 59) ductal, 7.5% (n = 5) lobular and 4.5% (n = 3) other. Significant associations were found between: A) Overall grade III–IV toxicity: TP53 rs1045522 [10.8% (n = 4) GG vs. 43.3% (n = 13) GC/CC, p = 0.004]; DNA repair gene XPC rs2228001 [8.7% (n = 2) AA vs. 34.1% (n = 15) AC/CC, p = 0.037]. B) Anaemia grade II–IV: ERCC2 rs1799793 [7.1% (n = 2) GG vs. 33.3% (n = 13) GA/AA, p = 0.016]; XPC rs2228001 [4.3% (n = 1) AA vs. 31.8% (n = 14) AC/CC, p = 0.012]. C) Neutropenia grade II–IV: C YP2C8 rs1341164 [6.5% (n = 2) TT vs. 27.8% (n = 10) TC/CC, p = 0.028]; TP53 rs1045522 [8.1% (n = 3) GG vs. 30.0% (n = 9) GC/CC, p = 0.027]; XPC rs2228001 [0.0% AA vs. 27.3% (n = 12) AC/CC, p = 0.006]. D) Diarrhoea grade II–IV: ABCB1 rs1128503 [21.4% (n = 6) TT vs. 2.6% (n = 1) TC/CC, p = 0.018]; CYP1B1 rs72549389 [20.0% (n = 7) TT vs. 0% TG/GG, p = 0.014]. No associations with neurotoxicity were found. Conclusions: Studying genetic variations can help to identify patients at higher risk of suffering adverse events and provides useful information to individualise therapy. No conflict of interest.