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. Here, CHEK2 is linked to breast cancer.