SP4.5 Expression of trans-membrane mucins is associated with poor outcomes after chemotherapy in breast cancer

Abstract Aims Chemoresistance is a key barrier to breast cancer cures, particularly in the triple-negative subtype. Mucins are O-glycosylated proteins that may drive therapeutic resistance and oncogenic progression in carcinomas. Somatic mutations in mucin 3 (MUC3), 12 (MUC12) and 16 (MUC16) have been identified in breast tumour samples, however their impacts on chemoresponse are poorly explored. We aimed to explore whether breast cancer cell expression of transmembrane mucins MUC3, MUC12 and MUC16 correlates with chemotherapy outcomes. Methods Immunohistochemistry was performed on tissue microarrays of primary breast tumours resected from patients subsequently treated with adjuvant chemotherapy (n=303). Tumour cores were semi-quantitively scored based on proportion and intensity of tumour cells staining for MUC3, MUC12 and MUC16. Receiver Operating Characteristic curves were used to dichotomize into relatively high and low expressing groups. Kaplan-Meier analyses were used to determine correlations with disease-free or overall survival. Results Relatively high expression of MUC3 was significantly associated with poor outcomes after adjuvant cytotoxic chemotherapy, in terms of shorter disease-free (p=0.001) and overall survival (p=0.016). Interestingly, higher expression of MUC3 was also associated with this apparent chemoresistance in the triple-negative breast cancer subtype specifically, with reduced disease-free (p=0.041) and overall survival (p=0.032). High expression of structurally-related mucins MUC12 or MUC16 also showed possible weak trends towards poor outcomes after chemotherapy, although significance was not reached. Conclusions In the future, mucins may offer promise as novel predictive biomarkers, or as targets for inhibition using monoclonal antibodies, for example, to enhance chemoresponse and improve survival outcomes in breast cancer patients.