A 48-year-old woman from Mumbai undergoes staging for a grade 3 invasive ductal carcinoma of the breast (Stage IIIA: T3N1M0). HER2 testing is positive (3+ on immunohistochemistry). Which drug is the drug of choice for HER2-targeted neoadjuvant therapy in this patient?

Explanation

## HER2-Targeted Therapy in Locally Advanced Breast Cancer **Key Point:** Trastuzumab is the drug of choice for HER2-positive breast cancer, including neoadjuvant settings in locally advanced disease. **Mechanism:** - Monoclonal antibody against HER2 receptor - Induces antibody-dependent cellular cytotoxicity (ADCC) - Inhibits HER2 signalling and cell proliferation - Improves pathological complete response (pCR) when combined with chemotherapy **Evidence & Dosing:** - **Neoadjuvant regimen**: Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 3 weeks × 6 cycles concurrent with chemotherapy (e.g., AC-TH: doxorubicin/cyclophosphamide followed by docetaxel + trastuzumab) - HERA trial and subsequent studies show improved disease-free survival and overall survival in HER2-positive breast cancer - pCR rates increase from ~25% (chemotherapy alone) to ~40–50% (chemotherapy + trastuzumab) **Clinical Pearl:** Trastuzumab requires baseline and periodic cardiac monitoring (LVEF/echocardiography) due to risk of cardiotoxicity; contraindicated if baseline LVEF <50%. **High-Yield:** HER2 status (not hormone receptor status) determines trastuzumab eligibility; it is effective regardless of ER/PR status.