Targeting the tumor microenvironment in triple-negative breast cancer: Biological insights and therapeutic opportunities

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Despite initial chemosensitivity, TNBC often relapses, and nearly half of patients develop distant metastases, particularly to visceral organs and the brain. In recent years, growing attention has been given to the tumor microenvironment (TME) as a critical driver of disease progression, immune evasion, and therapeutic resistance. TME is composed of a dynamic network of immune and stromal cells, extracellular matrix components, and soluble mediators that influence tumor behavior and shape response to treatment. In this review, we provide a comprehensive overview of the cellular and molecular composition of the TME in TNBC, highlight key prognostic and predictive markers, and discuss emerging therapeutic strategies aimed at targeting TME components. Understanding the complex crosstalk between the tumor and its microenvironment is essential for developing effective, personalized approaches to managing TNBC in the future.