NR4A1 and breast cancer: For instance, hypermethylation-mediated loss of the tumor suppressor TGFBI gene correlates with trastuzumab-resistance in HER2+ BC subtypes [87]; hypermethylation of MSH2 and hypomethylation of chemoresistance-related genes (MDR1, MGMT, GSTP, and UPA) are linked to doxorubicin-resistance in luminal A and TNBC subtypes [88,89]; while hypermethylation of CYP1B1 promoter is a highly significant predictor of tamoxifen-resistance as it reduces activation of tamoxifen into its active metabolites in both hormone receptor-positive and hormone receptor-negative subtypes [90].