{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:16:07Z","timestamp":1780406167204,"version":"3.54.1"},"reference-count":100,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cl\u00ednica M\u00e9dica Sur Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer remains the most frequently diagnosed malignancy among women worldwide, while metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease, reflecting a global burden of metabolic dysfunction. Increasing evidence suggests that MASLD is associated with breast cancer development and progression; however, whether this relationship reflects an independent effect of hepatic metabolic dysfunction or the broader metabolic environment remains uncertain. This review synthesizes current epidemiological, clinical, and mechanistic data linking hepatic metabolic dysfunction to breast carcinogenesis. Population-based studies consistently demonstrate an association between hepatic steatosis and increased breast cancer incidence, particularly in postmenopausal and metabolically vulnerable populations, as well as poorer oncological outcomes. Mechanistically, MASLD promotes a systemic pro-tumorigenic environment through interconnected pathways, including insulin resistance, hormonal dysregulation with increased estrogen bioavailability, chronic inflammation, oxidative stress, lipid metabolic reprogramming, and gut\u2013liver axis disruption. Hepatokines, particularly fibroblast growth factor 21 (FGF21), emerge as key mediators of tumor progression and potential biomarkers of metabolic vulnerability, while Fetuin-A and angiopoietin-like protein 8 (ANGPTL8) further support the liver\u2019s endocrine role in oncogenic signaling. Preclinical evidence highlights fatty acid oxidation as a metabolic dependency in aggressive breast cancer subtypes, suggesting novel therapeutic targets. Despite consistent associations, causality remains unproven. Future prospective studies are needed to determine whether targeting metabolic dysfunction can improve breast cancer prevention and outcomes.<\/jats:p>","DOI":"10.3390\/ijms27114919","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breast Cancer and Metabolic Dysfunction-Associated Steatotic Liver Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-7525","authenticated-orcid":false,"given":"Damaris G.","family":"Nieva-Ram\u00edrez","sequence":"first","affiliation":[{"name":"Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, Mexico City Z.C. 14050, Mexico"},{"name":"School of Medicine, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 13 Sur 2702, Los Volcanes, Puebla Z.C. 72420, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Luna-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, Mexico City Z.C. 14050, Mexico"},{"name":"School of Medicine, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 13 Sur 2702, Los Volcanes, Puebla Z.C. 72420, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-7869","authenticated-orcid":false,"given":"Misael","family":"Uribe","sequence":"additional","affiliation":[{"name":"Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, Mexico City Z.C. 14050, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Nu\u00f1o-L\u00e1mbarri","sequence":"additional","affiliation":[{"name":"Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, Mexico City Z.C. 14050, Mexico"},{"name":"Department of Surgery, Faculty of Medicine, The National Autonomous University of Mexico (UNAM), Mexico City Z.C. 04360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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