Abstract 430: Precision diet and lipid modulating agents to induce lipid oxidation in breast cancer

Abstract Metastasis is the primary cause of breast cancer-related mortality, and understanding the intricate relationship between the tumor microenvironment, lipid metabolism, and metastasis is crucial for preventing cancer progression. Previous work from our group demonstrated that high exogenous levels of oleic acid, a monounsaturated fatty acid (MUFA), in the lymph node environment protects melanoma cells from ferroptosis. Ferroptosis is an iron-dependent form of cell death induced by accumulation of lipid peroxides, which are commonly formed from polyunsaturated fatty acids (PUFAs), but not MUFAs. Here, we hypothesized that increasing dietary PUFAs would alter the exogeneous lipid content of the lymph node environment, thus rendering breast cancer cells more sensitive to ferroptosis. To test this, we determined the in vitro sensitivity of 4T1 triple negative breast cancer cells to ferroptosis when treated with various PUFAs and MUFAs. We also assessed the impact of various PUFA and MUFA fatty acid-enriched diets on breast cancer metastasis and ferroptosis resistance in the lymph nodes in vivo. In concordance with previously published work, our results demonstrated that pharmacological induction of ferroptosis in vitro increased lipid oxidation and was mitigated by fatty acid treatments with higher MUFA compared to PUFA content. In vivo, cancer cells in lymph nodes of mice on palm oil diets had lower lipid oxidation compared to cancer cells from tumors in the mammary fat pad. These findings support the hypothesis that dietary lipids can alter ferroptosis response and the extent of lipid oxidation in breast cancer cells within lymph nodes. Our research has the potential to further reveal mechanistic connections between dietary lipids, the lymphatic microenvironment, and breast cancer progression. Citation Format: Mahsa Yavari, Jordan Torpey, Marie Sabatier, Alanis Carmona, Krystina Szylo, Midori Flores, Mario Palma, Cameron Fraser, Yanshan Liang, Sheng Tony Hui, Oana Zeleznik, Heather Eliassen, Jessalyn Ubellacker. Precision diet and lipid modulating agents to induce lipid oxidation in breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 430.