HER2

HER2 (Human Epidermal Growth Factor Receptor 2)

• Type: A transmembrane receptor tyrosine kinase (part of the EGFR family).
• Gene: ERBB2 gene on chromosome 17.
• Role: Regulates cell growth, survival, and differentiation via intracellular signaling pathways (e.g., PI3K/AKT, MAPK).
• Overexpression/Amplification:
  • Found in approximately 15-20% of breast cancers, also seen in gastric, esophageal, and some other cancers.
  • Leads to aggressive tumor growth and worse prognosis if untreated.
• Testing:
  • IHC (Immunohistochemistry): Measures HER2 protein overexpression on the cell membrane.
  • FISH (Fluorescence In Situ Hybridization): Detects gene amplification.
  • HER2-positive defined by IHC 3+ or FISH amplification.

Clinical relevance

• Targeted therapies: Drugs that inhibit HER2 are key in treating HER2-positive cancers.
  • Examples: Trastuzumab, Pertuzumab, T-DM1 (ado-trastuzumab emtansine), Fam-trastuzumab deruxtecan (Enhertu), Neratinib.
• Mechanism: These agents block HER2 signaling, inhibit tumor cell proliferation, and mediate antibody-dependent cellular cytotoxicity (ADCC).
• Monitoring: Cardiotoxicity is a key adverse effect, especially with trastuzumab; baseline and periodic LVEF assessment recommended.