An endocrine microbe immunity framework for granulomatous mastitis toward phenotype-oriented interpretation

Granulomatous mastitis (GM) is a heterogeneous inflammatory breast disease that remains difficult to define, diagnose, and manage. Variability in terminology, diagnostic criteria, and reported etiologic associations has fragmented understanding of its pathogenesis. This review synthesizes current clinical, pathological, microbiological, and immunological evidence and proposes an endocrine-microbe-immunity (EMI) framework as an integrative, non-causal, hypothesis-generating model. Within this framework, endocrine-associated signals (e.g., hyperprolactinemia), phenotype-linked microbial findings (e.g., Corynebacterium in selected subsets), and immune-associated inflammatory features are treated as co-occurring, context-dependent domains whose relative contributions vary across phenotypes, rather than a fixed causal sequence. This perspective frames GM as a clinical spectrum and supports a phenotype-oriented approach, including a network-informed diagnostic strategy and phenotype-aware therapy. Given the predominantly retrospective, heterogeneous evidence, the EMI framework is offered as a heuristic structure. Future progress requires standardized phenotyping and prospective, phenotype-stratified studies with meaningful outcomes such as time to remission and recurrence.