This prospective study of 1,038 Chinese women with HR-positive, HER2-negative early-stage breast cancer provided novel insights into the comprehensive relations of the 21-gene RS and the ΔCt values of cancer-related genes with metabolic factors and biomarkers of insulin and the IGF axis, and the prognostic impact of the 21-gene RS in subgroups stratified by the metabolic factors and insulin and the IGF axis biomarkers. Here, INS is linked to breast cancer.