title: Prognostic and predictive value of thymidine phosphorylase activity in early-stage breast cancer patients.
abstract: The antitumor effects of 5-fluorouracil (5-FU) and its derivatives depend upon the activity of nucleoside metabolic enzymes in tumor tissues. Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine, to 5-FU. The relationship between TP expression in tumor tissues and patient survival was retrospectively examined in early-stage breast cancer patients treated with either oral 5'-DFUR administered for 6 months or surgery alone in a prospective randomized controlled trial. Thymidine phosphorylase expression in tumor cells and tumor-associated stromal (TAS) cells was examined by immunohistochemistry in 650 tissue samples from patients in this trial (n = 1217). Eight-year follow-up data showed that high TP expression in tumor cells was a significant prognostic indicator of a favorable outcome only for the patients in the 5'-DFUR group. Thus, TP expression was shown to be a predictive factor of 5'-DFUR efficacy. Conversely, a low TP expression in TAS cells was also a potent favorable prognostic indicator. These results on TP status in 2 tumor cell types could provide novel information for predicting prognosis for a patient subgroup, which would receive a probable therapeutic effect from 5'-DFUR, and presumably, from adjuvant therapy of capecitabine in early-stage breast cancer. Determination of TP status might also identify a patient subgroup whose prognosis is quite favorable even without adjuvant therapy. Further investigations on prognostic and predictive implications of TP activity in a clinical setting are warranted.
authors.affiliation: Breast Cancer Center, Toyosu Hospital, Showa University School of Medicine, Koto-ku, Tokyo, Japan. t-tominaga@hkg.odn.ne.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tominaga
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Osahiko
authors.initials: O
authors.lastname: Abe
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; C025034:doxifluridine