Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

1000 Background: Neuropathy, one of the most common toxicities associated with taxane therapy, may be severe, function-limiting, and sometimes irreversible. Established predictors for increased risk include advanced age, diabetes, and type/dose/schedule of taxane. No established biomarkers have been identified to predict patients at greatest risk. Methods: E5103 is a randomized phase III trial comparing standard adjuvant chemotherapy for patients with early stage breast cancer with the same chemotherapy plus concurrent bevacizumab or concurrent and sequential bevacizumab. All 3 arms include weekly paclitaxel for 12 weeks. A GWAS was performed using the Infinium Human Omni1 array on 2204 patients. The primary hypothesis was to identify SNPs associated with time to report of first grade 2−4 neuropathy. SNP data underwent rigorous review to assess both SNP and sample quality. Analyses were performed using Cox regression model including established clinical trial covariates. Bonferroni corrections for multipl...