Dual targeting of HER2 signaling with trastuzumab and tyrosine kinase inhibitor lapatinib is used to treat patients with locally advanced HER2+ BC (168) and has been shown to inhibit HER2 mediated downstream signaling cascades via PI3K/Akt and MAPK/ERK activation in HER2+ BC (169). This evidence concerns the gene ERBB2 and breast cancer.