title: Thymidylate synthase and thymidine phosphorylase as predictive markers of capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer.
abstract: OBJECTIVE
  The primary purpose of this study was to evaluate the role of thymidylate synthase (TS) and thymidine phosphorylase (TP) as biomarkers to predict clinical outcomes of capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC).
  
  
  METHODS
  Of the patients who were previously treated with anthracycline and taxane regimens, 90 patients who had available tissue block for immunohistochemistry with measurable lesions were included. All patients received capecitabine (2,500 mg/m(2)/day) for 14 days every 3 weeks.
  
  
  RESULTS
  High TS expression was more common among patients with triple-negative (TN) subtype than among patients with other subtypes (33% for hormone receptor+, 8% for HER2+, and 58% for TN, P = 0.023). The median PFS was significantly lower in patients with high TS (6.6 vs. 3.0 months; P = 0.017) and low TP expressions (6.0 vs. 3.3 months; P = 0.013). A high TS and a low TP expressions were identified as unfavorable independent risk factors for PFS to capecitabine monotherapy in multivariate analysis (hazard ratio [HR], 1.7, P = 0.037 for high TS score; HR, 1.8, P = 0.014 for low TP score).
  
  
  CONCLUSIONS
  Our data suggest that high TS and low TP scores correlate with a shorter PFS for capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Yoon La
authors.initials: YL
authors.lastname: Choi
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D013939:Thymidine Phosphorylase / Q000032:analysis*; D013940:Thymidylate Synthase / Q000032:analysis*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D013939:Thymidine Phosphorylase; D013940:Thymidylate Synthase; C508053:ERBB2 protein, human