Cancer-Associated Adipocytes and Breast Cancer: Intertwining in the Tumor Microenvironment and Challenges for Cancer Therapy

SIMPLE SUMMARY: Breast cancer is the most prevalent cancer in women worldwide, and it exhibits a growing incidence. An increasing number of studies showed the complex bidirectional regulation between breast cancer and adjacent cancer-associated adipocytes. The present review summarizes the mechanisms of cancer-associated adipocyte formation in the breast cancer tumor microenvironment and the effect of cancer-associated adipocytes on the tumorigenesis, progression, and metastasis of breast cancer. We focused on the therapeutic resistance of breast cancer caused by cancer-associated adipocytes and potential strategies targeting cancer-associated adipocytes in breast cancer treatment. ABSTRACT: Adipocytes are the main components in breast tissue, and cancer-associated adipocytes (CAAs) are one of the most important components in the tumor microenvironment of breast cancer (BC). Bidirectional regulation was found between CAAs and BC cells. BC facilitates the dedifferentiation of adjacent adipocytes to form CAAs with morphological and biological changes. CAAs increase the secretion of multiple cytokines and adipokines to promote the tumorigenesis, progression, and metastasis of BC by remodeling the extracellular matrix, changing aromatase expression, and metabolic reprogramming, and shaping the tumor immune microenvironment. CAAs are also associated with the therapeutic response of BC and provide potential targets in BC therapy. The present review provides a comprehensive description of the crosstalk between CAAs and BC and discusses the potential strategies to target CAAs to overcome BC treatment resistance.