ESR1 and breast neoplasm: However DNMT1 and DNMT3A have been found to be only modestly overexpressed at lower frequencies.15,16 Up regulation of DNMT3B is dramatically associated with a higher histopathological grade of breast tumors as well as proliferation of marker Ki67 and negative estrogen receptor-α expression – all indicative of possible DNMT3B involvement in breast tumor progression and metastasis.17