Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative resistance to tamoxifen therapy in hormone receptor positive breast cancer.
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.
Reimer
Toralf
T
Department of Obstetrics & Gynaecology, University of Rostock, Faculty of Medicine, Germany. toralf.reimer@med.uni-rostock.de
Koczan
Dirk
D
Müller
Heiner
H
Friese
Klaus
K
Thiesen
Hans-Jürgen
HJ
Gerber
Bernd
B
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
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