Abstract P3-01-24: Triple negative and non-triple negative breast cancer have distinct metabolic characteristics associated with divergent survival outcomes

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with high histologic grade and poor prognosis. TNBC is also known to be associated with modified metabolic activities of both tumor and stromal cells in the tumor microenvironment, potentially as a mechanism to enhance tumor development and survival in low-nutrient conditions. Here we aimed to investigate the differences in the metabolic activity of TNBC vs. non-TNBC and their impact on survival. Methods: Comprehensive immune profiling, including the expression of 395 immune-associated genes measured by RNA-seq, and PD-L1 expression testing by IHC, was performed on 149 real-world breast cancer samples. 52 samples were, by definition, triple negative for ER, PR, and HER2 overexpression. Based on Reactome pathway database data, mRNA expression signatures of carbohydrate (7 genes), lipid (10 genes), protein (29 genes), vitamin/cofactor (6 genes), and overall (32 genes) metabolism were calculated by averaging the normalized gene expression of each gene set. Samples were grouped into high (greater than or equal to median expression) and low (less than median expression) groups for each metabolic signature. Statistical comparisons of biomarkers between groups were performed using the Wilcoxon Rank-Sum test for continuous variables and Fisher’s Exact Test for categorical variables (p≤0.05 for significance). Survival differences were quantified by Kaplan-Meier analysis (p≤0.05 for significance). Results: In general, TNBC demonstrated greater overall metabolic activity (p=0.001), including greater lipid (p=5.8×10-5), protein (p=0.0053), and vitamin/cofactor (p=0.04) metabolism. However, there was no significant difference in carbohydrate metabolism between TNBC and non-TNBC. Among TNBC cases, only higher vitamin and cofactor metabolism was associated with better overall survival (OS) (61 months vs. 37 months, p=0.029), while carbohydrate, lipid, protein, and overall metabolic activity were not significantly associated with OS. For non-TNBC cases, high overall metabolic activity was associated with better OS (180 months vs. 78 months, p=0.011), as was high carbohydrate (147 months vs. 79 months, p=0.0053), high lipid (162 months vs. 73 months, p=0.016), and high protein metabolism (148 months vs. 73 months, p=0.026). Conclusions: We found that, in general, TNBC is more metabolically active than non-TNBC, though the survival effects of this difference vary depending on the specific aspect of cellular metabolism being measured, with some signatures associated with OS in TNBC and others in non-TNBC. An improved understanding of the metabolic environment of breast cancer as it relates to both triple negative status and differences in patients may facilitate a more nuanced characterization of tumor subtypes, aiding in the development of treatment strategies taking this aspect of the tumor microenvironment into account.Citation Format: Sarabjot Pabla, Shipra Gandhi, Maria-Fernanda Senosain, Hardik Parikh, Erik Van Roey, Shuang Gao, Yamuna Pulivendula, Paul DePietro, Jeffrey M. Conroy, Stephanie B. Hastings, Kyle C. Strickland, Rebecca A. Previs, Eric Severson, Brian J. Caveney, Marcia Eisenberg, Taylor J. Jensen, Shakti Ramkissoon, Heidi Ko. Triple negative and non-triple negative breast cancer have distinct metabolic characteristics associated with divergent survival 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 P3-01-24.

Duke Scholars

Author Brian James Caveney Family Medicine and Community Health, Occupational & Environ ...