ERBB2 and neoplasm: In preclinical models, the combination of entinostat and AI therapy significantly reduced tumor volume in letrozole-resistant mouse xenograft models when compared to treatment with either agent alone.13 Mechanistic studies revealed that the HDAC inhibitor increased expression of ER and aromatase activity but downregulated HER2, and also phosphorylated HER2/MAPK and AKT.