ESR1 and breast cancer: While MBD information was unavailable for patients in our cohort and in the TCGA dataset, Sun et al.26 previously reported that the Active extratumoral subtype, which is associated with poorer overall survival among ER+ breast cancer patients25 and also expressed higher levels of Cluster 1 genes (Supplementary Fig. 3g), was associated with significantly lower MBD than the Inactive subtype.