Unraveling the use of vaccine therapy in HER-2 positive breast cancer: a comprehensive review of current state and future perspectives

Abstract

Despite significant advances in early detection and therapeutic strategies, breast cancer (BC) continues to pose a major public health challenge. The treatment of HER2-positive (HER2 +) BC has evolved substantially over recent years with the advent of monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody–drug conjugates (ADCs). Clinical progress has been significantly accelerated by a deeper understanding of the immune-regulatory properties of this subtype and its interactions with the tumor microenvironment. Despite the availability of effective HER2-targeted therapies, approximately one-third of patients develops resistance, highlighting the need for novel and more durable treatment strategies. Indeed, while current treatments have shown promising efficacy by promoting a “passive immune response,” they are associated with the emergence of resistant clones. Conversely, vaccine-based therapies are designed to elicit a durable “active immune response” by presenting tumor-associated antigens that stimulate the host immune system to recognize and eliminate malignant cells. This approach has the potential to generate long-lasting immunological memory, preventing recurrence, disease progression, and the emergence of immune-evasive tumor variants. This review provides a comprehensive overview of cancer vaccines strategies for HER2 + BC with emphasis on their mechanisms, advantages, limitations, and their current developmental status. We explore diverse delivery platforms, including peptide/protein-based, nucleic acid, and cell-based vaccines. The clinical utility of these strategies is assessed across different disease settings: from prevention and interception in pre-invasive lesions, to the (neo)adjuvant treatment of early-stage BC and the management of advanced metastatic disease. While advanced-stage BC often presents an immunosuppressive tumor microenvironment that hinders vaccine efficacy, early-stage disease offers a more favorable immunological milieu for inducing robust and durable T-cell responses. Furthermore, we discuss emerging innovations such as neoantigen discovery, next-generation adjuvants (e.g., TLR and STING agonists), and novel combinatorial approaches with checkpoint inhibitors to overcome immune evasion. Although most BC vaccines remain under clinical investigation, they represent a promising frontier for achieving disease control and the coming decade is expected to yield pivotal insights into their clinical utility and therapeutic potential.