{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:26:33Z","timestamp":1787401593426,"version":"build-2736575974"},"reference-count":156,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","award":["3332025004"],"award-info":[{"award-number":["3332025004"]}],"id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ferroptosis, an iron\u2010dependent form of regulated cell death driven by lipid peroxidation, has emerged as a potential therapeutic vulnerability in breast cancer. However, increasing evidence indicates that ferroptosis sensitivity is not solely determined by tumour\u2010intrinsic factors, but is dynamically regulated by the tumour microenvironment (TME), particularly through interactions among adipocytes, immune cells and iron metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>\n                      Recent studies provide mechanistic evidence for this context dependence. Adipocyte\u2010derived monounsaturated fatty acids such as oleic acid suppress lipid peroxidation and increase resistance to ferroptosis induction in triple\u2010negative breast cancer, whereas ACSL4\u2010driven polyunsaturated phospholipid remodelling enhances ferroptosis susceptibility. In parallel, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell\u2010derived interferon\u2010\u03b3 promotes ferroptosis by suppressing SLC7A11\u2010mediated cystine uptake, while tumour\u2010associated macrophages buffer oxidative stress through iron sequestration and glutathione\u2010dependent antioxidant programs. These opposing forces indicate that ferroptosis is governed by a coordinated adipocyte\u2013immune\u2013iron regulatory network rather than a single pathway. Unlike previous reviews focused mainly on tumour\u2013intrinsic mechanisms or general TME effects, this review integrates adipocyte\u2010derived lipid metabolism, immune\u2010mediated redox regulation, iron handling and spatial heterogeneity into a unified \u2018ferroptosis ecosystem\u2019 framework. Based on this concept, we propose eco\u2010ferrotherapy, a translational strategy aimed at simultaneously targeting tumour\u2010intrinsic pathways and microenvironmental buffering systems. This framework may support subtype\u2010specific therapeutic prioritisation, biomarker\u2010guided patient stratification and rational combination strategies involving immunotherapy and nanomedicine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ferroptosis in breast cancer should be understood as an ecosystem\u2010level vulnerability shaped by metabolic, immune and spatial factors. Defining and therapeutically targeting this ferroptosis ecosystem provides a conceptual and translational roadmap for improving precision treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70707","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:43:13Z","timestamp":1780382593000},"source":"Crossref","is-referenced-by-count":1,"title":["Ferroptosis in breast cancer: From adipocyte\u2013immune\u2013iron regulation to therapeutic application"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-1208","authenticated-orcid":false,"given":"Juan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Breast Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Dongcheng District Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Dongcheng District Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Dongcheng District Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Dongcheng District Beijing 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