Modulating N1 and N2 neutrophils in breast cancer: potential therapeutic approaches - a narrative review

Neutrophils play a dual role in breast cancer progression, acting as anti-tumorigenic (N1) or pro-tumorigenic (N2) subtypes based on cues from the tumor microenvironment (TME). This review examines the mechanisms driving neutrophil polarization, focusing on how the TME promotes N2 dominance to support tumor growth, angiogenesis, and metastasis. Therapeutic strategies targeting these processes, including cytokine modulation, immune checkpoint inhibitors, and small-molecule drugs, are discussed. Emerging insights into neutrophil biology highlight the potential to reprogram N2 neutrophils into N1 phenotypes, offering promising avenues for enhancing cancer immunotherapy and improving breast cancer outcomes. Neutrophils are critical components of the tumor microenvironment, influencing breast cancer progression through distinct subtypes: anti-tumorigenic N1 and pro-tumorigenic N2 neutrophils. This review delves into the polarization of neutrophils by tumor-derived factors and their contrasting roles in breast cancer biology. N2 neutrophils drive angiogenesis, immunosuppression, and metastasis, while N1 neutrophils counteract these processes. Current therapeutic approaches, including TGF-β inhibitors, chemokine modulation, and immune checkpoint therapies, aim to shift the balance toward N1 neutrophils.