Advances in the role of tumor-associated neutrophils in the development of breast cancer

Neutrophils originate from the bone marrow, differentiating from hematopoietic stem cells, and are the most prevalent polymorphonuclear leukocytes in the blood, accounting for approximately 70% of the total white blood cells in adult peripheral blood. Neutrophils are recognized as one of the relatively short-lived cells in the body, with a normal half-life of just a few hours in the peripheral blood, which rely on continuous replenishment from the bone marrow to maintain the number. As short-lived effectors of the innate immune system, neutrophils participate in various inflammatory and immune processes, and constitute the first line of defense against infection, playing a crucial role in the activation and regulation of both innate and adaptive immunity. Neutrophils were once considered as key effectors of inflammation and infection. Because of their short lifespan and non-proliferative nature, the role of neutrophils in cancer was overlooked. Their role in cancer has been increasingly recognized in recent years. However, more and more studies demonstrate that neutrophils play a much more significant role in cancer than previously thought. Breast cancer is one of the common malignant tumors in women, and its morbidity and mortality are in the forefront of female malignant tumors. The incidence of breast cancer is rising globally, posing a severe threat to the physical and mental health of women worldwide. Recent studies confirm that tumor-associated neutrophils (TANs) have become a critical component of the tumor microenvironment (TME) and play a significant role in the development, progression and metastasis of breast cancer. TANs are formed via the interaction of various tumor-derived cytokines which stimulate and recruit neutrophils to accumulate in the TME. The strong plasticity and diversity of neutrophils endow TANs with dual potential to both promote and inhibit tumors. TANs advance breast cancer progression by promoting tumor growth and metastasis, supporting tumor angiogenesis, immune suppression, and generating neutrophil extracellular traps (NETs). Conversely, TANs mediate antitumor responses through direct tumor cell killing and contributing to the formation of antitumor immune network. Research on TANs-related breast cancer therapies, particularly in triple-negative breast cancer (TNBC), has become a research hotspot. This review summarized recent advances in the origin, formation, classification and function of TANs in breast cancer, as well as a detailed discussion of their clinical relevance. We further combined recent clinical studies to systematically summarize the treatment strategies targeting TANs in breast cancer, with the aim of providing new insights into the functional mechanisms of TANs and the treatment of breast cancer.