Our findings suggest that patients with highly proliferative (high MKS or high GGI) and high-ER breast cancers (high expression of ER-related genes both adopted from Oncotype DX or from PAM50) have the highest absolute risk for late relapse tumors, despite the fact that their risk of recurrence is modest in the first 5 years on tamoxifen. Here, ESR1 is linked to breast carcinoma.