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Summary: Despite adjuvant chemotherapy and endocrine therapy in luminal breast cancer (LBC), relapses are common. Addressing this, we aim to develop a prognostic model to refine adjuvant therapy strategies, particularly for patients at high recurrence risk. Notably, obesity profoundly affects the tumor microenvironment (TME) of LBC. However, it is unclear whether obesity-related biological features can effectively screen high-risk patients. Utilizing weighted gene coexpression network analysis (WGCNA) on RNA sequencing (RNAseq) data, we identified seven obese LBC genes (OLGs) closely associated with patient prognosis. Subsequently, we developed a luminal obesity-gene clinical prognostic index (LOG-CPI), combining a 7-gene signature, TNM staging, and age. Its predictive efficacy was confirmed across validation datasets and a clinical cohort (5-year accuracy = 0.828, 0.760, 0.751, and 0.792, respectively). LOG-CPI emerges as a promising predictor for clinical prognosis and treatment response, helping distinguish molecular and immunological features in LBC patients and guiding clinical practice by identifying varying prognoses. |