The HER2 family and interrelated signaling and events. The binding of ligands, including epidermal growth factor and transforming growth factor-α, leads to the activation of signaling cascades involving Ras/Raf/MAPK, PI3K/Akt/mTOR, and JAK/STAT. This sequence of events promotes the apoptosis, proliferation, survival, migration, angiogenesis, and metastasis of HER2-over-expressing breast cancers. BTC, betacellulin; EGF, epidermal growth factor; EPG, epigen; EPR, epiregulin; HB-EGF, heparin-binding EGF-like growth factor; HER, human epidermal growth factor receptor; JAK, Janus kinase; JNK, c-Jun N-terminal kinase 1; mTOR, mammalian target of rapamycin; MAPK, mitogen-activated protein kinase; MEK, mitogen-induced extracellular kinase; MEKK, mitogen-activated protein/ERK kinase kinase; NRG, neuregulin; PI3K, phosphatidylinositol 3-kinase; STAT, signal transducer and activator of transcription; TGF, transforming growth factor; TK, tyrosine kinase.