Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer
B V Sinn, G von Minckwitz, C Denkert, H Eidtmann, S Darb-Esfahani, H Tesch, R Kronenwett, G Hoffmann, A Belau, C Thommsen, H J Holzhausen, S T Grasshoff, K Baumann, K Mehta, M Dietel, S Loibl, B V Sinn, G von Minckwitz, C Denkert, H Eidtmann, S Darb-Esfahani, H Tesch, R Kronenwett, G Hoffmann, A Belau, C Thommsen, H J Holzhausen, S T Grasshoff, K Baumann, K Mehta, M Dietel, S Loibl
Abstract
Background: Mucin-1 (MUC1) is a promising antigen for the development of tumor vaccines. We evaluated the frequency of MUC1 expression and its impact on therapy response and survival after neoadjuvant chemotherapy for breast cancer.
Patients and methods: Pre-treatment core biopsies of patients from the GeparTrio neoadjuvant trial (NCT 00544765) were evaluated for MUC1 by immunohistochemistry (IHC; N = 691) and quantitative RT-PCR (qRT-PCR; N = 286) from formalin-fixed paraffin-embedded (FFPE) samples.
Results: MUC1 protein and mRNA was detectable in the majority of cases and was associated with hormone-receptor-positive status (P < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (P = 0.017 and P < 0.001) and with longer patient survival (P = 0.03 and P < 0.001). In multivariable analysis, MUC1 protein and mRNA expression were independently predictive (P = 0.001 and P < 0.001). MUC1 protein and mRNA expression were independently prognostic for overall survival (P = 0.029 and P = 0.015).
Conclusions: MUC1 is frequently expressed in breast cancer and detectable on mRNA and protein level from FFPE tissue. It provides independent predictive information for therapy response and survival after neoadjuvant chemotherapy. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.
Trial registration: ClinicalTrials.gov NCT00544765.
Keywords: Mucin-1; breast cancer; neoadjuvant chemotherapy; pCR; prognosis.
Source: PubMed