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 ].
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