Neoantigen-driven personalized vaccines for breast cancer: Platforms, nano-delivery systems, and combination strategies.

Breast cancer (BC) is the most common malignancy among women globally. Despite significant advances, therapeutic resistance and tumor recurrence remain major clinical challenges. Personalized cancer vaccines have recently emerged as a promising strategy to induce durable, highly specific anti-tumor immune responses and improve long-term survival. However, challenges persist in neoantigen prediction, vaccine formulation, and practical implementation, which can hinder the overall effectiveness and widespread adoption of these personalized cancer vaccines. Ongoing technological advancements are expected to facilitate the development of more efficient and accessible personalized vaccines for BC. This review systematically summarizes recent progress in personalized BC vaccines, focusing on neoantigen identification, emerging vaccine platforms, nano-delivery systems, and subtype-specific vaccine strategies. It also discusses the pharmacological basis of these vaccines, including immune activation mechanisms, pharmacokinetic influences on efficacy, and mechanisms of vaccine resistance. Furthermore, we explore combination strategies integrating cancer vaccines with immune checkpoint inhibitors (ICIs), radiotherapy, and chemotherapy to overcome the immunosuppressive tumor microenvironment (TME) and enhance therapeutic efficacy. Ultimately, this review provides a comprehensive reference to guide future research and promote the clinical translation of personalized vaccine-based immunotherapies for breast cancer.