Furthermore, in METABRIC, we found that high TmS is associated with improved DFS for patients with ER+HER2− breast cancer, after adjusting for chemotherapy and Oncotype Dx risk status (n = 1,100, HR = 0.74, 95% CI: 0.60, 0.91, log-rank P = 0.004; Fig. 4i and Supplementary Table 7). This evidence concerns the gene ESR1 and breast cancer.