P53 GENE ALTERATIONS ARE ASSOCIATED WITH A DECREASED RESPONSIVENESS TO NEOADJUVANT CHEMOTHERAPY IN HUMAN BREAST-CANCER

Recent evidence indicates that alterations of the p53 tumor suppressor gene can modulate the response of tumor cells to DNA-damaging agents and increase drug resistance. To evaluate whether p53 alterations affe ct response to chemotherapy in breast cancer, we examined the p53 stat us before and after treatment of primary tumors from 44 patients who r eceived neoadjuvant chemotherapy. p53 status was determined by gene mu tations and by mRNA expression levels. Eleven patients (25%) showed al terations in the p53 gene. Comparison of the clinical response between subgroups with or without p53 alterations revealed that p53 alteratio ns were strongly associated to clinical resistance to chemotherapy (p< 0.001).