Breast Cancer Vaccines and Combination Immunotherapy: Current Evidence, Limitations and Future Directions
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Background: Breast cancer is the most commonly diagnosed cancer in women worldwide and a leading cause of cancer mortality. Despite advances in targeted therapy, immunotherapy has yielded modest gains, constrained by the immunosuppressive tumour microenvironment (TME) and molecular heterogeneity across subtypes such as triple-negative breast cancer (TNBC) and HER2-positive disease. This review evaluated the clinical efficacy of current breast cancer vaccine platforms and examined whether combination immunotherapy strategies overcome TME-mediated immune suppression.
Methods: A PRISMA-ScR-guided scoping review was conducted across Scopus, PubMed, Google Scholar, Web of Science, and African Journals Online up to 30 April 2026. Of 2,334 records identified, 307 duplicates were removed, and remaining studies were screened by two independent reviewers. Following full-text assessment of 298 reports, 49 studies met eligibility criteria and were included. Quality was appraised using the CASP tool, and findings were synthesised thematically.
Results: Vaccine platforms showed limited durable efficacy as monotherapy. Key barriers included low tumour-infiltrating lymphocyte density, checkpoint upregulation, antigen escape, and TME-driven metabolic suppression. Regulatory approval remains restricted to TNBC in PD-L1-positive metastatic (KEYNOTE-355) and high-risk early-stage (KEYNOTE-522) settings. Combination regimens integrating checkpoint inhibitors, chemotherapy, HER2-directed agents, or PARP inhibitors improved outcomes, albeit with immune-related toxicity. Personalised neoantigen vaccines and biomarker-guided selection emerged as promising near-term strategies.
Conclusion: Vaccine monotherapy cannot overcome TME-mediated immunosuppression. Combination approaches pairing immune priming with checkpoint blockade, targeted therapy, or immunogenic chemotherapy offer the greatest clinical promise, contingent on refined biomarker selection, reduced toxicity, and equitable vaccine access.
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