The search terms used included the following combined subject headings: HER2-positive breast cancer, herceptin, trastuzumab, resistance, p95HER2, phosphatidylinositol 3-kinase (PI3K)/Akt, phosphatase and tensin homolog (PTEN), HER3, insulin-like growth factor 1 receptor (IGF-1R), angiogenesis, lapatinib, pertuzumab, trastuzumab-DM1 (T-MD1), HER2 tyrosine kinase inhibitors (TKIs), heat-shock protein (HSP) 90 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, IGF-1R inhibitors, and bispecific antibodies. This evidence concerns the gene PTEN and breast cancer.