tokens: Analyzing tumor samples from a total of 109 primary locally advanced breast cancer patients treated with epirubicin 90mg / 3 weekly , we found TP53 mutations affecting the L2 / L3 domains or protein dimerization , as well as non - functional CHEK2 mutations abrogating dimerization and phosphorylation , to be associated with therapy resistance ; no mutation or promoter hypermethylations of the p14 ( ARF ) gene was discovered .