Among various multigene prognostic gene assays, the 21-gene RS assay has been more widely used in patients who are classified as early stage according to AJCC TNM 8th edition, have ER + /HER2- breast cancer, or are to be spared from unnecessary adjuvant chemotherapies as recommended by the NCCN guidelines when detected with low RS [7]. The gene discussed is ESR1; the disease is breast cancer.