Exhaustive single nucleotide polymorphism (SNP) analysis of DPYD exome in breast cancer patients (pts) receiving capecitabine.

2571 Background: Consensual DPYD variants *2A, D949V and I560S are associated with fluoropyrimidine toxicity (Caudle, CPT 2013). Full sequencing of DPYD exome was conducted in a prospective cohort of advanced breast cancer pts receiving capecitabine (88.5% monotherapy) to examine relationships between DPYDSNPs and toxicity. Methods: 243 over 303 pts included in 12 French institutions were analyzed. Digestive, neurologic and hematotoxicity over cycles 1-2 showed 10.3% G3 (25 pts) and 2.1% G4 (5 pts), including one toxic death. DPYD exome along with flanking intronic regions (20 bp), 3’UTR and part of 5’UTR (500 bp upstream transcription initiation) were sequenced on MiSeq Illumina (Integragen, PCR multiplex, 97% coverage on average, HWE checked). Results: In addition to consensual variants *2A, D949V and I560S carried by 7 pts (all heterozygous), 45 SNPs were identified: 7 in 3’UTR, 17 in coding regions (4 synonymous including E412E; 13 missenses including V732I, R592W, I543V, S534N, S492L, M406I, D342G, M...