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Here, we developed a butyrate metabolism\u2010specific gene (BMRG) signature to predict clinical outcomes and immunotherapy responses in BC, providing a novel pathway\u2010focused prognostic tool. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we identified 102 butyrate metabolism\u2010related differentially expressed genes (DEGs) through the intersection of DEGs, WGCNA\u2010derived key module genes, and BMRGs. Univariate Cox followed by least absolute shrinkage and selection operator (LASSO) analysis identified nine genes to construct a prognostic signature, which served as an independent prognostic factor. Risk stratification revealed distinct immune microenvironment and mutation landscapes between subgroups, with risk scores strongly correlating with immune checkpoint expression. The signature exhibited robust prognostic performance, with AUC values for 3\u2010, 5\u2010, and 7\u2010year overall survival ranging from 0.65\u20130.69 in TCGA and 0.57\u20130.77 in independent GEO cohorts. Protein\u2013protein interaction analysis identified ACSL1 as a key hub gene, and functional validation confirmed that ACSL1 knockdown suppressed BC cell proliferation and migration. Our findings establish this novel nine\u2010gene butyrate metabolism\u2010specific signature as a promising prognostic biomarker and potential therapeutic target for BC, providing a metabolism\u2010focused perspective for personalized BC management.<\/jats:p>","DOI":"10.1002\/cam4.71763","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:41:58Z","timestamp":1774586518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Butyrate Metabolism\u2010Related Gene Signature Predicts Prognosis, Immune Landscape, and Immunotherapy Efficacy in Breast Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Xu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital  Zhengzhou 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