Neutrophil-driven tumor inflammation in breast cancer: Pathways and therapeutic implications: A narrative review

Neutrophils, a key component of the innate immune system, have emerged as significant players in the tumor microenvironment (TME) of breast cancer. Traditionally recognized for their role in defending against infections, neutrophils in cancer contribute to both tumor progression and suppression, depending on their activation state and the signals they receive. Neutrophil-driven inflammation within the TME is critical in promoting tumor growth, metastasis, and resistance to treatment. This review explores the complex role of neutrophils in breast cancer, emphasizing the mechanisms through which they influence tumor inflammation, including their interactions with other immune cells and the signaling pathways involved. Neutrophils can either support tumor progression by releasing pro-inflammatory cytokines, enzymes, and reactive oxygen species, or contribute to antitumor responses by directly killing cancer cells and stimulating adaptive immunity. The balance between these opposing functions is heavily influenced by the TME's cytokine milieu and neutrophil polarization. Key signaling pathways, such as the CXCR2-CXCL8 axis and interactions with tumor-associated macrophages, regulate neutrophil recruitment and activation in the TME, enhancing inflammation and tumorigenesis. Additionally, neutrophils' ability to form neutrophil extracellular traps further complicates their role, potentially promoting metastasis by trapping circulating tumor cells.