Herceptin

Trastuzumab is a monoclonal antibody that binds to the extracellular domain of HER2 (human epidermal growth factor receptor 2), a receptor tyrosine kinase overexpressed in ~20-25% of breast cancers due to ERBB2 gene amplification. HER2 overexpression drives increased cell proliferation and is associated with more aggressive tumor behavior. Trastuzumab works by multiple mechanisms: blocking HER2 dimerization and downstream signaling (PI3K/AKT and MAPK pathways), inducing antibody-dependent cellular cytotoxicity (ADCC), and preventing HER2 receptor cleavage. Clinical use requires confirmation of HER2 positivity via immunohistochemistry (IHC 3+) or fluorescence in situ hybridization (FISH) amplification, as only HER2-positive tumors respond. It is used in both adjuvant and metastatic settings for breast cancer, often combined with chemotherapy (e.g., paclitaxel), and also in HER2-positive gastric/gastroesophageal junction cancers. A key adverse effect is cardiotoxicity, presenting as a reversible dilated cardiomyopathy with decreased left ventricular ejection fraction (LVEF), distinct from the irreversible, dose-dependent cardiotoxicity seen with anthracyclines like doxorubicin. This is thought to result from blocking HER2-mediated repair/survival signaling in cardiomyocytes, which is important during cardiac stress (e.g., after anthracycline use). Due to this overlapping cardiotoxic risk, combination with anthracyclines requires careful cardiac monitoring (echocardiography/MUGA scan) before and during treatment. Other adverse effects include infusion reactions, pulmonary toxicity, and rarely, oligohydramnios/fetal renal problems if used during pregnancy. Trastuzumab represents a classic example of targeted/precision oncologic therapy exploiting a specific molecular alteration (HER2 amplification) for improved efficacy and defines a key USMLE testable concept: distinguishing trastuzumab-induced (reversible) vs. anthracycline-induced (irreversible) cardiotoxicity.