Immunomodulatory Effects of Breast Cancer Therapies: Unraveling the Crosstalk Between Therapeutics and the Tumor Immune Microenvironment

Breast cancer is a heterogeneous malignancy that consists of multiple molecular subtypes, each requiring therapeutic approaches distinctively. While traditional treatments, including endocrine therapy, and anti-HER2 therapy, primarily targeting on cancer cell proliferation and survival, emerging evidence underscores their profound immunomodulatory effects within the tumor microenvironment. The intricate interplay between breast cancer treatments and immune cells shapes therapeutic efficacy and patient outcomes. This review aiming to analysis the immunomodulatory functions of various therapies, including selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and CDK4/6 inhibitors; monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs); and the role of PARP inhibitors, PI3K inhibitors, and mTOR inhibitors in modulating immune responses. We discuss how these treatments impact key immune populations, including tumor-infiltrating lymphocytes, myeloid-derived suppressor cells (MDSCs), and natural killer (NK) cells, as well as their influence on immune checkpoints and cytokine signaling pathways. Understanding the dual role of breast cancer therapies in both suppressing tumor growth and modulating the immune landscape offers new opportunities for strategies integrating targeted therapy and immunotherapy. By elucidating these interactions, we aim to provide insights into optimizing treatment strategies to enhance antitumor immunity and improve patient prognosis.