LAUSR

Triple Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype with poor prognosis, partly due to its heterogenous molecular profile. Unlike other breast cancer subtypes, targeted therapies for TNBC are lacking, highlighting an urgent need for a better understanding of the underlying biology of the disease that can be used to develop more effective, tailored therapies. In this study, changes in glycosylation of TNBC primary tumors were analyzed in order to gain better insight into the biology of the disease with the goal of pinpointing specific glycan structures that might be useful as diagnostic and prognostic biomarkers that could assist in early detection, risk assessment and creating personalized treatments. Our past work studying glycosylation in breast cancer has linked specific glycan structural classes to different tissue regions, including stromal, necrotic and tumor areas. Fucosylation, a specific form of glycosylation, influences various immune and hormonal physiological processes and is frequently expressed by tumors. Previous studies by others have linked core fucosylation to increased proliferation, metastatic potential and therapeutic resistance in a variety of cancers, including breast cancer. Further, we have reported that tumor-associated core-fucosylated polylactosamine glycans are significantly more prevalent in metastatic breast cancers compared to non-metastatic ones. The present study utilizes MALDI Imaging Mass Spectrometry to elucidate the spatial distribution of core-fucosylated N-glycans in TNBC tissues and assess their correlation with clinical outcome, tumor stage and patient survival status. Tissue samples were from female TNBC patients that self-identified as African ancestry (n=79). Tissues were previously banked for all research purposes and not specifically for this study; MUSC IRB approval as exemption #4. Clinical data includes tumor stage and grade, tumor nuclear grade, receptor status, metastatic sites, histology, surgical plan, chemotherapy status, BMI, age, and family history of cancer. Data showed that core fucosylation associated with stage of TNBC, with increases in stage III (ANOVA ≤0.001). By random forest machine learning, a set of three core fucosylated glycans were the primary differentiating factors in discriminating between stages of TNBC. We further found 9 specific core-fucosylated N-glycans that associated with survival status in the cohort (5-year survival n=39 alive; n=41 deceased; Kaplan-Meier (Log-Rank Mantel Cox test) p-value ≤0.01, Hazard ratio ≥2.5. In summary, our analysis revealed that TNBC tumors with high levels of core fucosylation were frequently associated with advanced cancer stage and poor patient outcomes, including reduced overall survival. Further studies are warranted to explore the mechanistic role of these glycans in TNBC progression. The association between increased core fucosylation and adverse clinical outcomes underscores the potential utility for targeting core fucosylation, either alone or in combination with immune-stimulating therapies, to improve outcomes for TNBC patients. Citation Format: Jaclyn Dunne, Laura Spruill, Taylor Hulahan, Graham Colditz, Anand S. Mehta, Richard R. Drake, Marvella Ford, Peggi M. Angel. Linking Spatial Distribution of Core Fucosylated N-Glycans to Triple Negative Breast Cancer Outcomes [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-01-23.