As mutations in the phosphatidylinositol 3 kinase (PIK3CA) exons 9 and 20 gene and/or loss of the tumor suppressor gene PTEN occurs frequently in breast cancer with over-expression of HER-2 and is associated with a poorer outcome and relative trastuzumab resistance, investigations into blocking this pathway in combination with trastuzumab have been investigated. The gene discussed is ERBB2; the disease is breast carcinoma.