Targeted Therapy and Immunotherapy for Heterogeneous Breast Cancer

SIMPLE SUMMARY: Breast cancer (BC) is a common malignancy with molecular diversity, i.e., heterogeneity. Aside from routine clinical treatments, such as chemotherapy and radiotherapy, which have side effects and tumor resistance, troubling patients and doctors, targeted therapy based on molecular classifications and immunotherapy with novel approaches to reprogram the immune system offer solutions to improve prognosis, anti-tumor efficacy, and address drug resistance. Here, we review the wide range of molecular classifications of heterogeneous BC, emphasize targeted therapy and immunotherapy, and provide insights into the significance of targeted drug delivery systems. ABSTRACT: Breast cancer (BC) is the most common malignancy in women worldwide, and it is a molecularly diverse disease. Heterogeneity can be observed in a wide range of cell types with varying morphologies and behaviors. Molecular classifications are broadly used in clinical diagnosis, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and breast cancer gene (BRCA) mutations, as indicators of tumor heterogeneity. Treatment strategies differ according to the molecular subtype. Besides the traditional treatments, such as hormone (endocrine) therapy, radiotherapy, and chemotherapy, innovative approaches have accelerated BC treatments, which contain targeted therapies and immunotherapy. Among them, monoclonal antibodies, small-molecule inhibitors and antibody–drug conjugates, and targeted delivery systems are promising armamentarium for breast cancer, while checkpoint inhibitors, CAR T cell therapy, cancer vaccines, and tumor-microenvironment-targeted therapy provide a more comprehensive understanding of breast cancer and could assist in developing new therapeutic strategies.