AbstractPurposeConstituting 15 to 20% of breast cancer cases, the triple-negative subtype lacks effective treatments as being less responsive to hormone-associated therapies. Alternatively, a more powerful immunotherapeutic vaccination can trigger immune recognition and destruction against breast cancer by incorporating oncological antigens such as human epidermal growth factor receptor 2 (HER2/neu). Currently, HER2/neu-based vaccines have finished three phases with breast cancer patients, in conjunction with granulocyte-macrophage colony-stimulating factor (GM-CSF) that was proven to be a promising vaccine adjuvant in other cancer trials previously.MethodsCompleted HER2/neu-based vaccine trials with GM-CSF immunoadjuvants for breast cancer were summarised, and additionally, the article discussed prominent findings of vaccine effectiveness in triple-negative breast cancer, regarding li-Key hybrid in vaccine design and co-administration of anti-HER2/neu trastuzumab.ResultsNine clinical trials of three HER2/neu epitopes, one with li-Key hybrid, were analysed with or without the presence of trastuzumab. Immunological responses and minimal toxicities were observed in these epitopes, and disease-free survival was especially improved in the triple-negative population.ConclusionHER2/neu-based peptide vaccine is a safe and effective approach against breast cancer, and its benefits can be potentially furthered by combining the li-Key hybrid vaccine with targeted drugs and adjuvants selected to enhance cross-presentation for exogenous vaccine antigens.Graphical abstract