title: Modulation of thymidine phosphorylase by neoadjuvant chemotherapy in primary breast cancer.
abstract: The combination effect of docetaxel and capecitabine on tumour response rate and survival was demonstrated recently in metastatic breast cancer patients. This combination was based on an experimental hypothesis that taxane can increase tumour sensitivity to the effect of capecitabine through the upregulation of thymidine phosphorylase (TP), which is responsible for the metabolism of 5-fluorouracil (5-FU) and its derivatives, including capecitabine. To examine the alteration in TP expression before and after neoadjuvant chemotherapy, 92 patients with primary breast cancer (T2-4N0-1M0) were enrolled in this study; 14 were treated with adriamycin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC); 58 with 5-FU, adriamycin, and cyclophosphamide (FAC) or 5-FU, epirubicin, and cyclophosphamide (FEC); and 20 with FEC followed by docetaxel/taxotere (TXT-containing regimen). Thymidine phosphorylase upregulation was seen in 54.4% and 32.6% of patients in tumour cells and stromal cells, respectively. Increases in TP expression were found only in the AC/EC and TXT-containing regimen groups. In conclusion, it was strongly suggested that unlike 5-FU-containing regimens, the taxane and AC combination therapies upregulate TP expression in primary breast cancer. Thymidine phosphorylase upregulation by several anticancer drugs implies the importance of individualised strategies for sensitisation of tumour tissues to 5-FU and its derivatives.
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. maktoi77@wa2.so-net.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Toi
authors.forename: H
authors.initials: H
authors.lastname: Bando
authors.forename: S
authors.initials: S
authors.lastname: Horiguchi
authors.forename: M
authors.initials: M
authors.lastname: Takada
authors.forename: A
authors.initials: A
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Ueno
authors.forename: S
authors.initials: S
authors.lastname: Saji
authors.forename: M
authors.initials: M
authors.lastname: Muta
authors.forename: N
authors.initials: N
authors.lastname: Funata
authors.forename: S
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D043823:Taxoids / Q000008:administration & dosage; D013939:Thymidine Phosphorylase / Q000096:biosynthesis* / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D013939:Thymidine Phosphorylase; D005472:Fluorouracil