## HER2-Positive Breast Cancer: First-Line Targeted Therapy **Key Point:** Trastuzumab (Herceptin) is the gold-standard first-line monoclonal antibody for HER2-positive metastatic breast cancer, especially in treatment-naïve patients. ### Mechanism of Action Trastuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2 receptor, leading to: - Blockade of HER2 signaling - Antibody-dependent cellular cytotoxicity (ADCC) - Cell cycle arrest and apoptosis ### First-Line Regimen Trastuzumab is typically combined with: - Chemotherapy (docetaxel or paclitaxel) for initial treatment - Pertuzumab (dual HER2 blockade) in some protocols - Continued as maintenance monotherapy after chemotherapy completion **High-Yield:** Trastuzumab monotherapy is approved for maintenance in HER2-positive metastatic breast cancer after chemotherapy, with median overall survival benefit of 2–3 years. ### Cardiac Monitoring **Warning:** Trastuzumab carries a 5–7% risk of left ventricular dysfunction (cardiomyopathy). Baseline and periodic echocardiography or MUGA scan is mandatory. ### Comparison with Other HER2-Directed Agents | Agent | Role | Indication | |-------|------|------------| | Trastuzumab | First-line monoclonal antibody | HER2+ metastatic BC, all lines | | Pertuzumab | Second HER2-binding epitope | Dual blockade (added to trastuzumab) | | T-DM1 | Antibody-drug conjugate | Second-line or beyond | | Lapatinib | Tyrosine kinase inhibitor | Brain metastases, HER2+ gastric cancer | **Clinical Pearl:** In treatment-naïve HER2-positive metastatic breast cancer, trastuzumab + chemotherapy remains the standard of care, with response rates >80% and median progression-free survival of 12–15 months. [cite:Harrison 21e Ch 397]
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