Figure 4.

Integrative model linking breastfeeding, microbiota, and TNBC protection. This conceptual framework illustrates how breastfeeding practices shape the breast and milk microbiota, influencing host immune, inflammatory, and metabolic pathways that ultimately affect TNBC risk. Prolonged breastfeeding promotes the enrichment of beneficial taxa such as Lactobacillus and Bifidobacterium, which increase short-chain fatty acid (SCFA) production and contribute to a stable, diverse microbial community. These microbes support immune tolerance by enhancing regulatory T cells and anti-inflammatory cytokines (IL-10, TGF-β), reducing pro-inflammatory mediators (TNF-α, IL-6), maintaining epithelial barrier integrity, and exerting epigenetic control through HDAC inhibition. Together, these mechanisms reduce luminal progenitor expansion, inflammation, and DNA damage, thereby lowering TNBC risk. Conversely, absence of or abrupt cessation of breastfeeding is associated with dysbiosis, characterized by the enrichment of taxa such as Ralstonia, Bacillus, Staphylococcus, and Escherichia coli. These microbial profiles favor chronic inflammation, NF-κB/STAT3 activation, DNA damage, immune evasion, and metabolic dysregulation, leading to enhanced tumor progression and metastasis. The model highlights how the balance between prolonged breastfeeding with a healthy microbiota and short or absent breastfeeding with dysbiosis can tip the trajectory toward either protection or promotion of TNBC.