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Inflammation underlies the onset of the disease, and NF\u2010\u03baB is a master transcription factor for inflammation. Nuclear factor\u2010\u03baB (NF\u2010\u03baB) is activated in a variety of cell types, including normal epithelial cells, cancer cells, cancer\u2010associated fibroblasts (CAFs), and immune cells. Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer, and not all DCIS lesions develop into invasive breast cancers (IBC). Currently, most patients with DCIS undergo surgery with postoperative therapy, although there is a risk of overtreatment. In <jats:italic>BRCA<\/jats:italic> mutants, receptor activator of NF\u2010\u03baB (RANK)\u2010positive progenitors serve as the cell of origin, and treatment using the RANK monoclonal antibody reduces the risk of IBC. There is still an unmet need to diagnose malignant DCIS, which has the potential to progress to IBC, and to establish appropriate prevention strategies. We recently demonstrated novel molecular mechanisms for NF\u2010\u03baB activation in premalignant mammary tissues, which include DCIS, and the resultant cytokine\u2010enriched microenvironment is essential for breast cancer development. On the early endosomes in a few epithelial cells, the adaptor protein FRS2\u03b2, forming a complex with ErbB2, carries the I\u03baB kinase (IKK) complex and leads to the activation of NF\u2010\u03baB, thereby inducing a variety of cytokines. Therefore, the FRS2\u03b2\u2010NF\u03baB axis in the inflammatory premalignant environment could be targetable to prevent IBC. Further analysis of the molecular mechanisms of inflammation in the premalignant microenvironment is necessary to prevent the risk of IBC.<\/jats:p>","DOI":"10.1111\/cas.15734","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T07:30:14Z","timestamp":1674804614000},"page":"1792-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inflammatory cytokine\u2010enriched microenvironment plays key roles in the development of breast cancers"],"prefix":"10.1111","volume":"114","author":[{"given":"Yasuto","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Division of Cancer Cell Biology Cancer Research Institute, Kanazawa University  Kanazawa City Japan"},{"name":"Institute for Frontier Science Initiative, Kanazawa University  Kanazawa City 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