Abstract P2-06-09: Impact of lipid composition on triple-negative breast cancer progression and survival

Abstract Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, with high resistance to chemotherapy and low survival rates, and accounts for 10-15% of all breast cancer cases. TNBC incidence has been associated with obesity and fatty acids in the tumor microenvironment (TME) derived from lipids can induce obesity-driven metabolic inflammation and affect TNBC pathology. However, the unique impact of the TNBC subtype on lipid composition in the TME, and its subsequent role as an energy source for cancer cell metabolism and progression is unknown. Understanding lipid heterogeneity in the TME will provide novel insights to target TNBC. It is, therefore, crucial to understand the impact of TNBC-driven TME remolding in the context of lipid composition. Our study aims to decipher the role of lipid composition in the progression of TNBC. Spatial lipid profiling of hormone receptor-positive (HR+) and TNBC primary tumors was performed and compared to matched normal breast adipose tissue. Raman mapping of lipids showed a heterogeneous distribution of lipids across the TNBC tissues, including five omega-3 fatty acids, two omega-6 fatty acids, and one unsaturated fatty acid were upregulated in TNBC tumors compared to normal-matched adipose. To determine the unique impact of lipids elevated in TNBC, we next demonstrated that the uptake of lipid compounds (linoleic acid, docosahexaenoic acid, and oleate acid) by TNBC cells increased cell proliferation after 72 hours of treatment. Overall, our results suggest that lipid composition plays a key role in breast TME and may represent a novel therapeutic strategy to target TNBC by alternate sensitivity to therapeutic modalities including apoptosis and ferroptosis. Citation Format: Khudeja Salim, Elnaz Sheikh, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, Matthew E. Burow, Manas R. Gartia. Impact of lipid composition on triple-negative breast cancer progression and survival [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 P2-06-09.