With our preclinical study showing synergy between entinostat and anti-HER2 therapeutics as a scientific rationale, we conducted a phase Ib study investigating the novel combinations of entinostat and lapatinib plus/minus trastuzumab in patients with metastatic HER2+ breast cancer after progression during treatment with a trastuzumab combination regimen. Here, ERBB2 is linked to breast cancer.