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. CONCLUSION: 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