Mucin-1 protein and mRNA expression in breast cancer: Predictive value for therapy response and survival after neoadjuvant chemotherapy.

Abstract

522 Background: Mucin-1 (MUC1) is expressed in normal epithelial cells and in breast cancer. Immunotherapeutic agents targeting MUC1 are currently tested in clinical trials. Methods: We evaluated the frequency of MUC1 expression by immunohistochemistry (IHC; n = 691) and quantitative RT-PCR (qRT-PCR; n = 286) in formalin-fixed paraffin-embedded (FFPE) pre-treatment biopsies from patients of the GeparTrio trial (NCT 00544765). mRNA levels were analyzed as a continuous variable, a distribution-based cut-off was chosen for IHC data. The predictive value for therapy response and survival after neoadjuvant anthracycline/taxane-based chemotherapy (CTX) was evaluated. Results: MUC1 was detectable by IHC in 95%. qRT-PCR covered a dynamic range of 3 orders of magnitude. IHC and mRNA data were correlated (p < 0.001). MUC1 was detected in higher quantities in HR+ tumors (p < 0.001), the lowest levels were found in HR-/HER2- tumors (p < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (pCR) in the overall population (p < 0.001) and in HR+ (p = 0.004 and < 0.001), HER2- (p < 0.001) and HR+/HER2- tumors (p < 0.001). In multivariable logistic regression, MUC1 was independently predictive (high MUC1 protein: odds ratio (OR) 0.464, 95% CI 0.300 – 0.719, p = 0.001; MUC1 mRNA (per 20-dCT unit): OR 0.673, CI 0.546 – 0.829, p < 0.001). MUC1 protein and mRNA expression were associated with longer patient survival in the overall population (p = 0.03 and < 0.001) and in HER2- tumors (p = 0.005 and < 0.001). MUC1 mRNA was also prognostic in HR+ (p < 0.001) and HR+/HER2- tumors (p = 0.001). In multivariable analysis, protein and mRNA expression were independently prognostic (high MUC1 protein: hazard ratio (HR) 0.388, CI 0.166 – 0.907, p = 0.029; MUC1 mRNA per 20-dCT unit: HR 0.763, CI 0.595 – 0.909, p = 0.005). Conclusions: MUC1 is frequently expressed in breast cancer and detectable by IHC and qRT-PCR from FFPE tissue. Despite its association with HR+ status, it provides independent predictive information for therapy response and survival after neoadjuvant CTX. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.