docetaxel + doxorubicin + metformin + trastuzumab

This is a multi-agent combination regimen consisting of four drugs: - **Docetaxel** (a taxane-class chemotherapeutic that inhibits microtubule depolymerization, leading to cell cycle arrest and apoptosis), - **Doxorubicin** (an anthracycline antibiotic that intercalates DNA and inhibits topoisomerase II, causing DNA damage and cell death), - **Metformin** (a biguanide antidiabetic agent with emerging evidence for anti-cancer effects via inhibition of mitochondrial complex I, reduction of cellular proliferation, and modulation of metabolic pathways), and - **Trastuzumab** (a monoclonal antibody targeting the human epidermal growth factor receptor 2 [HER2], blocking HER2-mediated signaling in cancer cells). This combination has been investigated as neoadjuvant therapy for HER2-positive breast cancer. The rationale is to combine cytotoxic chemotherapy with targeted anti-HER2 therapy and potential metabolic modulation by metformin. Clinical studies have evaluated similar regimens—often substituting liposomal doxorubicin for conventional doxorubicin due to reduced cardiotoxicity—demonstrating safety and activity but not clear superiority over sequential regimens[1][2][7]. Metformin may enhance the efficacy of trastuzumab-based therapies by overcoming resistance mechanisms in HER2-positive tumors[10].