Which monoclonal antibody targets HER2 and is the standard first-line agent in HER2-positive metastatic breast cancer when combined with chemotherapy?

Explanation

## HER2-Targeted Therapy in Breast Cancer ### Trastuzumab: Anti-HER2 Monoclonal Antibody **Key Point:** Trastuzumab is a humanized monoclonal antibody that binds to the extracellular domain of HER2 (human epidermal growth factor receptor 2), blocking HER2 signaling and inducing antibody-dependent cellular cytotoxicity (ADCC) [cite:Harrison 21e Ch 88]. ### Mechanism of Action 1. **Direct binding** to HER2 extracellular domain 2. **Prevents heterodimerization** of HER2 with other ErbB receptors 3. **Induces ADCC** via Fc receptor engagement on immune cells 4. **Inhibits PI3K/AKT and MAPK pathways** downstream of HER2 ### Clinical Efficacy in HER2+ Breast Cancer - **First-line standard** in HER2-positive metastatic breast cancer (combined with chemotherapy, typically docetaxel or paclitaxel) - Improves overall survival and progression-free survival - Also used in HER2+ early-stage breast cancer (adjuvant setting) - IV infusion; loading dose 4 mg/kg, then 2 mg/kg weekly **High-Yield:** HER2 amplification/overexpression occurs in ~15–20% of breast cancers and is associated with aggressive behavior; trastuzumab is a landmark targeted therapy that transformed outcomes in this subset. ### Cardiac Toxicity **Warning:** Trastuzumab carries risk of **left ventricular dysfunction and heart failure**, especially when combined with anthracyclines. Baseline and periodic echocardiography or MUGA scan is mandatory. **Mnemonic:** **HER2-TRASTUZUMAB** = **H**umanized **E**xtra**R**cellular **2** antibody **T**argeting **R**eceptor **A**ctivity **S**ignaling **T**umor **U**pstream **Z**one **U**nder **M**onoclonal **A**ntibody **B**inding.