As shown in Fig. 2 and Table 2, we demonstrated that the germline-derived NOG_CSS significantly distinguished recurred and non-recurred breast tumors in two validations sets: 200 (ER+ Nature-Set, P = 1.4 × 10−2) and 295 (ER+ TCGA-CPTAC independent set, P = 1.4 × 10−3). This evidence concerns the gene ESR1 and breast neoplasm.