Altered Adipokine Expression in Tumor Microenvironment Promotes Development of Triple Negative Breast Cancer

SIMPLE SUMMARY: Obesity is highly associated with overall risk for breast cancer and correlated with aggressive behavior. Although recent advances indicated that increased BMI may be an important factor for triple negative breast cancer development, the molecular mechanisms have not been fully elucidated. Obesity predisposes to breast cancer via metabolic modifications of tumor microenvironment. Altered adipocyte accumulation results in secretion of inflammatory factors, chemokines and adipokines which establish a pro-tumorigenic microenvironment that stimulates breast cancer induction, evolution and metastasis and impede anti-cancer drug response. The present article focuses on the association between adipokine expression and breast cancer, particularly triple negative subtype, and provides a summary and critical presentation of novel research findings. The main effort is to better determine strategies for tumor stratification and management. ABSTRACT: Obesity is a remarkably important factor for breast carcinogenesis and aggressiveness. The implication of increased BMI in triple negative breast cancer (TNBC) development is also well established. A malignancy-promoting role of the adipose tissue has been supposed, where the adipocytes that constitute the majority of stromal cells release pro-inflammatory cytokines and growth factors. Alterations in adipokines and their receptors play significant roles in breast cancer initiation, progression, metastasis, and drug response. Classic adipokines, such as leptin, adiponectin, and resistin, have been extensively studied in breast cancer and connected with breast cancer risk and progression. Notably, new molecules are constantly being discovered and the list is continuously growing. Additionally, substantial progress has been made concerning their differential expression in association with clinical and pathological parameters of tumors and the prognostic and predictive value of their dysregulation in breast cancer carcinogenesis. However, evidence regarding the mechanisms by which adipose tissue is involved in the development of TNBC is lacking. In the present article we comment on current data on the suggested involvement of these mediators in breast cancer development and progression, with particular emphasis on TNBC, to draw attention to the design of novel targeted therapies and biomarkers.