Breast cancer vaccines for treatment and prevention.

Breast cancer is immunogenic and a variety of vaccines have been designed to boost immunity directed against the disease. The components of a breast cancer vaccine, the antigen, the delivery system, and the adjuvant, can have a significant impact on vaccine immunogenicity. There have been numerous immunogenic proteins identified in all subtypes of breast cancer. The majority of these antigens are weakly immunogenic nonmutated tumor-associated proteins. Mutated proteins and neoantigen epitopes are found only in a small minority of patients and are enriched in the triple negative subtype. Several vaccines have advanced to large randomized Phase II or Phase III clinical trials. None of these trials met their primary endpoint of either progression-free or overall survival. Despite these set-backs investigators have learned important lessons regarding the clinical application of breast cancer vaccines from the type of immune response needed for tumor eradication, Type I T-cell immunity, to the patient populations most likely to benefit from vaccination. Many therapeutic breast cancer vaccines are now being tested in combination with other forms of immune therapy or chemotherapy and radiation. Breast cancer vaccines as single agents are now studied in the context of the prevention of relapse or development of disease. Newer approaches are designing vaccines to prevent breast cancer by intercepting high-risk lesions such as ductal carcinoma in situ to limit the progression of these tumors to invasive cancer. There are also several efforts to develop vaccines for the primary prevention of breast cancer by targeting antigens expressed during breast cancer initiation.