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This review delineates a novel mechanistic framework wherein CRC\u2010driven dysregulation of the brain\u2013gut\u2013microbiota axis (BGMA) acts as a systemic architect of the breast pre\u2010metastatic niche (PMN). We synthesize how localized intestinal oncogenic stress propagates through three convergent conduits: (1) Immune Reprogramming, where gut\u2010derived inflammatory mediators and extracellular vesicles (EVs) recruit myeloid\u2010derived suppressor cells (MDSCs) to the mammary stroma; (2) Neuro\u2010ecological Conditioning, involving chronic hypothalamic\u2013pituitary\u2013adrenal (HPA) axis activation and sympathetic hyperactivation that drives catecholamine\u2010mediated remodeling of breast tissue; and (3) Humoral\u2010Metabolic Convergence, specifically via the \u201cestrobolome\u201d and secondary bile acids that synchronize systemic hormonal levels with local tissue receptivity. By reframing CRC progression as a systemic pathology that potentially preconditions distant, hormone\u2010sensitive environments, we propose the BGMA as a conceptual framework for prospective \u201csystemic interception\u201d, outlining roadmaps to neutralize metastatic cascades at their incipient, reversible stages.<\/jats:p>","DOI":"10.1002\/ijc.70681","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:26:12Z","timestamp":1792495572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Intestinal Origins to Mammary Targets: Exploring the Potential Role of the Brain\u2010Gut\u2010Microbiota Axis in Pre\u2010Metastatic Conditioning of Breast Tissue in Colorectal Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1770-5043","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Northern Jiangsu People's Hospital Affiliated to Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327736"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21772"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2025-335412"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00934-z"},{"issue":"2","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s00432-023-05518-z","article-title":"Patterns and Trends of Mortality From Metastatic Colorectal Cancer in Shanghai, China From 2005 to 2021: A Population\u2010Based Retrospective Analysis","volume":"150","author":"Cheng X.","year":"2024","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02729-7"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01937-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-013-9420-1"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003"},{"issue":"8","key":"e_1_2_11_11_1","article-title":"The Intestinal Microbiome and Estrogen Receptor\u2010Positive Female Breast Cancer","volume":"108","author":"Kwa M.","year":"2016","journal-title":"Journal of the National Cancer Institute"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6467"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2019"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"S301","DOI":"10.21037\/jgo-2019-gi-04","article-title":"The Brain\u2010Gut Axis in Gastrointestinal Cancers","volume":"12","author":"Alpert O.","year":"2021","journal-title":"Journal of Gastrointestinal Oncology"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.100829"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.14.1685"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2006.11.006"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104958"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0237-2"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-24-00088"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2647"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1460493","article-title":"The Sympathetic Nervous System Shapes the Tumor Microenvironment to Impair Chemotherapy Response","volume":"14","author":"Manoleras A. 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