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 affect response to chemotherapy in breast cancer, we examined the p53 status before and after treatment of primary tumors from 44 patients who received neoadjuvant chemotherapy. p53 status was determined by gene mutations and by mRNA expression levels. Eleven patients (25%) showed alterations in the p53 gene. Comparison of the clinical response between subgroups with or without p53 alterations revealed that p53 alterations were strongly associated to clinical resistance to chemotherapy (p<0.001).