## HER2-Targeted Monoclonal Antibody Therapy **Key Point:** Trastuzumab (Herceptin) is a humanized monoclonal antibody that binds to the extracellular domain of HER2 (human epidermal growth factor receptor 2), blocking ligand-independent signaling and inducing antibody-dependent cellular cytotoxicity (ADCC). ### Mechanism of Action 1. **Receptor blockade:** Prevents HER2 homodimerization and heterodimerization 2. **ADCC induction:** Recruits natural killer cells and macrophages to destroy HER2-expressing tumor cells 3. **Cell cycle arrest:** Inhibits downstream PI3K/Akt and MAPK signaling ### Clinical Indications - **HER2-positive breast cancer** (early-stage and metastatic) - **HER2-positive gastric and gastroesophageal junction adenocarcinoma** - Improves overall survival when combined with chemotherapy **High-Yield:** HER2 positivity is defined as IHC 3+ or FISH amplification ratio ≥2.0. Trastuzumab is only effective in HER2-positive tumors. ### Cardiac Toxicity - **Major adverse effect:** Left ventricular ejection fraction (LVEF) decline - Risk increased with concurrent anthracyclines - Requires baseline echocardiography and periodic monitoring **Clinical Pearl:** Pertuzumab (another anti-HER2 antibody) is often used in combination with trastuzumab for synergistic effect by blocking different HER2 dimerization pathways. **Mnemonic:** **TRASH** = **T**rastuzumab targets **HER2** in breast and gastric cancers. [cite:Harrison 21e Ch 108]
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