To determine the importance of specific signaling molecules in HER2+ breast cancer cells that are sensitive to HER2 inhibitors or have been reported to be resistant, we evaluated a panel of inhibitors toward AKT, PLCγ, JNK, PI3K, SRC, mTORC1, p38, JAK, and c-RAF on BT474 (sensitive) and JIMT-1 (resistant) human breast cancer cells in an in vitro (2D culture) cell death analysis. This evidence concerns the gene AKT1 and breast cancer.