Tumor-Associated Neutrophils and Desmoplastic Reaction in the Breast Cancer Tumor Microenvironment: A Comprehensive Review

The evolving tumor microenvironment (TME) plays a critical role in breast cancer tumorigenesis, growth, and metastatic potential. This study focuses on two key components of the TME: tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR). We will analyze their multifaceted functions, emphasizing the significant mutual relationships among them, which dramatically affect disease outcomes and the effectiveness of treatments. TANs can either suppress or promote tumors, demonstrating notable functional flexibility in response to signals from their immediate environment. Concurrently, the proliferation of myofibroblasts and the extensive deposition of extracellular matrix (ECM), which characterize the DR, substantially alter the tumor's physical properties, increasing its stiffness. This increased stiffness significantly obstructs immune system cells from accessing the tumor, ultimately limiting the effectiveness of therapies and contributing to a more clinically aggressive tumor behavior. A comprehensive understanding of the interactions among TANs, the desmoplastic stroma, and other elements of the TME is critical for developing new predictive biomarkers and establishing more effective targeted therapies.