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Tumor Biology

SUN-299 - Dietary Lipids Skew Mast Cell Activity, Affecting Reemergence from Breast Cancer Dormancy

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Yifan Fei, MS: No financial relationships to disclose
Breast cancer is the second-leading cause of cancer-related death in women. Despite advancements in detection and treatment of the primary tumor, there are still over 168,000 women in the United States living with metastatic breast cancer. Cancer cells do not always proliferate after metastasis into distal sites but may remain dormant and “reawaken” later. The mechanisms initiating awakening are not fully understood.

Cholesterol is a dietary lipid that influences breast cancer progression and recurrence. Our group has shown that an oxidized cholesterol metabolite, 27-hydroxycholesterol, has a pro-metastatic effect on breast cancer. Therefore, we sought to elucidate the role oxidized lipids have on reemergence from breast cancer dormancy. As a test food relevant to American consumption, we utilized cured bacon. Bacon is high in fat and cholesterol, and commonly prepared by an oxidative cooking process (pan-frying). Strikingly, consumption of cured fried bacon fat (cfBF) resulted in a more rapid reemergence from dormancy compared to the control uncured fried bacon fat (ufBF) in vivo.

Mechanistically, we have found that metastatic tissues have reduced mast cell (MC) infiltration. Loss of MCs effects histaminergic signaling through the histamine 2 receptor (H2R). This loss results in priming neutrophils to form neutrophil extracellular traps (NETs) in a platelet-dependent manner. The increase in NET production was required for the effects of cfBF. These results support a novel Diet – MC – H2R – Platelet/Neutrophil-Dormancy axis.

To understand the trigger of recurrence via this axis, we performed lipid profiling of ufBF and cfBF, revealing different lipid composition in each diet, including an increase in oxidized sterols. Treating MCs with enriched cfBF lipids resulted in higher degranulation rates and altered expression of MC granule genes. This indicates one mechanism of recurrence is lipids depleting tissue MCs, resulting in lower histamine signaling, thereby sensitizing neutrophils to NETosis. Ongoing work centers on characterizing the effects of these lipids in vitro (MC function) and in vivo (recurrence). Taken together, our data highlight the impact of oxidized lipids on breast cancer recurrence through altered MC function and activity. This establishes a framework for the future development of novel therapeutic targets or lifestyle interventions to prevent recurrence.

Funded by the: American Institute for Cancer Research (713063), the National Cancer Institute (R01CA234025, R01CA288207) and Department of Defense Breast Cancer Research Program Era of Hope Scholar Award (BC200206). Further support to CPS from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (T32EB019944) and ATN from a National Institutes of Environment Health Sciences and Research Training in Toxicology and Environmental Health (T32ES007326).

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*