Novel Combination Therapies: A Game-Changer in Breast Cancer Treatment

Breast cancer remains the leading cause of cancer-related mortality among women, and therapeutic resistance continues to limit treatment success. This narrative review comprehensively explores the evolution and current landscape of combination therapies as a transformative strategy in breast cancer management. It integrates evidence from conventional multimodal regimens, such as surgery, radiotherapy, and chemotherapy, with emerging targeted, endocrine, and immunotherapeutic combinations that exploit synergistic molecular pathways. Special emphasis is placed on Bacteria-Mediated Cancer Therapy (BMCT), which utilises tumour-targeting bacterial vectors that preferentially colonise hypoxic areas of solid tumours, and nanotechnology-based drug delivery systems that enhance pharmacokinetics and enable tumour-selective targeting with reduced systemic toxicity. The review also examines the biological rationale, mechanisms of action, and clinical outcomes across breast cancer subtypes, while addressing challenges such as tumour heterogeneity, drug resistance, and treatment-related toxicity. Key findings indicate that rationally engineered combination therapies that integrate targeted or immunotherapeutic agents with nanocarrier or bacterial delivery platforms improve the therapeutic index, overcome monotherapy resistance and enable more tailored, subtype-specific treatment responses. Finally, it highlights future directions involving biomarker-driven, adaptive, and precision-based combination strategies, with the implication that these approaches are vital for personalizing therapy, reducing off-target toxicity and improving overall patient survival. Collectively, this review emphasizes combination therapy not merely as a marginal advance but as a paradigm shift toward more effective and individualized breast cancer treatment.