Immunogenic mutanome of breast cancer: Advances, challenges and future directions in neoantigen-based immunotherapy

Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for novel, more effective therapies. Neoantigen-based immunotherapy - which harnesses tumor-specific somatic mutations to boost immune recognition - has emerged as a particularly promising strategy. Advances in next-generation sequencing and computational immunopeptidomics now allow systematic mapping of the tumor mutanome and rapid identification of immunogenic neoantigens, enabling personalized vaccine design and more precise deployment of immune-checkpoint blockade. However, intratumor heterogeneity, immune-escape mechanisms and the often-limited intrinsic immunogenicity of individual neoepitopes continue to constrain clinical efficacy. This review synthesizes the current landscape of neoantigen-targeted immunotherapies in BC, outlines the principal obstacles to their broader impact and highlights emerging solutions - including improved epitope-prediction algorithms, multi-epitope vaccine constructs and synergistic combination regimens. A deeper understanding of the immunogenic mutanome is expected to translate into more durable and widely applicable treatments for patients with breast cancer.