ERBB2 and breast neoplasm: Moreover, other possible culprit mutations and pathways of resistance were also investigated with a notable role of KRAS mutations (85), and a major role of PI3K/AKT pathway, such as PIK3CA mutations that can occur in up to 40% of ER-positive, HER2- negative breast tumors, as well as RB1, ERBB2, FGFR2/3 mutations, and others.