Increased dihydropyrimidine dehydrogenase activity in breast cancer

Background and Objectives Although studies have focused on modulating the bioavailability of 5‐FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4‐fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P