Immunotherapy for HER2-Positive Breast Cancer: Clinical Evidence and Future Perspectives

Simple Summary Human epidermal growth factor receptor 2 (HER2) positive breast cancer is a heterogeneous disease. Among different therapeutic approaches, immunotherapies represent a relevant option for HER2-positive breast cancer patients, both in the adjuvant and metastatic setting. Starting from the dramatic clinical improvement observed with the advent of trastuzumab, which embodied a partly immune-mediated mechanism, a new wave of immunotherapies is now under investigation, including the novel HER2-directed monoclonal antibodies, the antibody-drug conjugates, the immune checkpoint inhibitors, the adoptive T-cell therapies, and therapeutic vaccines. In this narrative review, we present the most important clinical evidence on immunotherapy in HER2-positive breast cancer, and we critically discuss the uncertainties and opportunities in this evolving field of immune-oncology. Breast cancer is the most common malignancy among women worldwide, and HER2-positive breast cancer accounts for approximately 15% of all breast cancer diagnoses. The advent of HER2-targeting therapies has dramatically improved the survival of these patients, significantly reducing their risk of recurrence and death. However, as a significant proportion of patients ultimately develop resistance to these therapies, it is extremely important to identify new treatments to further improve their clinical outcomes. Immunotherapy has revolutionized the treatment and history of several cancer types, and it has already been approved as a standard of care for patients with triple-negative breast cancer. Based on a strong preclinical rationale, immunotherapy in HER2-positive breast cancer represents an intriguing field that is currently under clinical investigation. There is a close interplay between HER2-targeting therapies (both approved and under investigation) and the immune system, and several new immunotherapeutic strategies, including immune checkpoint inhibitors, CAR-T cells and therapeutic vaccines, are being studied in this disease. In this narrative review, we discuss the clinical evidence and the future perspectives of immunotherapy for patients with HER2-positive breast cancer.