Lower levels of EP300 and higher levels of the nuclear deacetylases, sirtuins (e.g., SIRT1 and SIRT6) were also detected in the BT474-LapR cells, which might also contribute to the reduced FOXO3 activity in BT474-LapR cells and therefore lapatinib resistance in HER2-positive breast cancer cells (Figure 1B). This evidence concerns the gene SIRT6 and breast cancer.