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Using murine models of mammary cancer dormancy, we found that a diet enriched with fat from fried, cured bacon (cfBF) decreased dormancy latency times. Resulting lesions had fewer mast cells (MCs). Loss of MCs alone resulted in reemergence from dormancy. Elevated expression of a MC gene signature in breast tumors was associated with improved progression free and overall survival, highlighting the human relevance of these findings. MCs are a major source of tissue histamine, and lesions from mice fed cfBF had decreased concentrations. Importantly, antagonists of the histamine receptor 2 (H\n                  <jats:sub>2<\/jats:sub>\n                  R) sparked reemergence from dormancy. H\n                  <jats:sub>2<\/jats:sub>\n                  R antagonists are over-the-counter drugs are taken to alleviate gastroesophageal reflux disease. Chronic treatment of mice with H\n                  <jats:sub>2<\/jats:sub>\n                  R-antagonists sensitized platelets towards activation and crosstalk with neutrophils, and subsequent formation of neutrophil extracellular traps (NETs). The loss of platelet or NETosis activity mitigated the H\n                  <jats:sub>2<\/jats:sub>\n                  R-antagonist stimulated reemergence from dormancy. Therefore, we establish a novel metastatic axis which links diet to recurrence via MCs, histaminergic signaling and NETosis: Diet -- MC -- H\n                  <jats:sub>2<\/jats:sub>\n                  R -- (\n                  <jats:italic>decreased<\/jats:italic>\n                  ) Platelet Activity -- (\n                  <jats:italic>decreased<\/jats:italic>\n                  ) Neutrophil-NETosis -- (\n                  <jats:italic>decreased<\/jats:italic>\n                  ) Reemergence from Dormancy. Our data reveal several potential intervention strategies: lifestyle, MC stabilization, histaminergic signaling, and neutrophil and platelet activity.\n                <\/jats:p>","DOI":"10.64898\/2026.04.14.718388","type":"posted-content","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:12Z","timestamp":1776297612000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1752-8829","authenticated-orcid":false,"given":"Claire P.","family":"Schane","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois Urbana Champaign, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-7835","authenticated-orcid":false,"given":"Adam 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