Granulomatous mastitis: from localized inflammation to systemic immune-mediated disorder

Granulomatous mastitis (GM) is a chronic inflammatory breast disease of unknown etiology, characterized by a high recurrence rate and challenging clinical management. This review reconceptualizes GM as an immune-mediated disorder and delineates the aberrant crosstalk between innate and adaptive immunity that constitutes its core pathogenesis. We emphasize that hyperprolactinemia acts as a pivotal driver, initiating a pro-inflammatory cascade characterized by macrophage M1 polarization, neutrophil extracellular trap (NET) release, NK cell activation, and severe disruption of T and B cell homeostasis. Currently, glucocorticoids (GCs) are routinely used in the treatment of Granulomatous mastitis, but their efficacy is limited and they cannot fulfill all the needs of clinical treatment. Therefore, it has become imperative to adopt immunomodulatory strategies for treatment. By synthesizing the evolving understanding of GM's immunopathology, this review aims to bridge the gap between mechanistic insights and clinical practice. We critically assess current and emerging therapeutics, including the potential role of Traditional Chinese Medicine (TCM), and propose a framework for future targeted therapeutic strategies that modulate specific immune pathways in GM.