title: Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative resistance to tamoxifen therapy in hormone receptor positive breast cancer.
abstract: BACKGROUND
  The objective of the present study was to examine the prognostic and predictive significance of the apoptosis-related marker Fas ligand (FasL):Fas ratio in breast cancer.
  
  
  METHODS
  Tumour biopsies from 215 primary invasive breast cancer patients were examined for the expression of FasL and Fas mRNA transcripts by quantitative real-time RT-PCR. Their prognostic and predictive impact on patient survival was determined in univariate and multivariate survival analyses.
  
  
  RESULTS
  Using a cutoff value of 1, a FasL:Fas ratio greater than 1 was found to have significant prognostic value for disease-free survival among the total population (median follow up 54 months). It was associated with a significantly decreased disease-free survival (P = 0.022) and with a tendency toward increased mortality (P = 0.14) in univariate analysis. Hormone receptor positive women exclusively treated with tamoxifen (n = 86) and with a FasL:Fas ratio greater than 1 had a significantly decreased disease-free survival (P = 0.008) and overall survival (P = 0.03) in univariate Kaplan-Meier analysis. Furthermore, tumour size and FasL:Fas ratio were of independent predictive significance in the multivariate model for disease-free and overall survival in that subgroup. Among postmenopausal patients (n = 148) both of those factors retained independent prognostic significance in the multivariate model for disease-free survival. In contrast, FasL:Fas ratio had no significant predictive value in patients exclusively treated with chemotherapy.
  
  
  CONCLUSIONS
  The data presented indicate that FasL:Fas ratio may be useful not only as a prognostic factor but also as a predictive factor for projecting response to the antioestrogen tamoxifen. The results strongly support a correlation between FasL:Fas ratio greater than 1 and lack of efficacy of tamoxifen in hormone receptor positive patients.
authors.affiliation: Department of Obstetrics & Gynaecology, University of Rostock, Faculty of Medicine, Germany. toralf.reimer@med.uni-rostock.de
authors.forename: Toralf
authors.initials: T
authors.lastname: Reimer
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Heiner
authors.initials: H
authors.lastname: Müller
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004965:Estrogen Antagonists; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019014:fas Receptor; D013629:Tamoxifen