Association of root canal bacteria with breast cancer: a systematic review and meta-analysis

Abstract Background Breast cancer, the most common malignancy in women worldwide, has been theorized to interact with oral pathogens like Fusobacterium nucleatum, Enterococcus faecalis, and Porphyromonas gingivalis —bacteria implicated in chronic inflammation and immune evasion in preclinical studies. However, human evidence remains inconsistent. Aims To systematically evaluate associations between these oral pathogens and breast cancer outcomes (incidence, progression, survival, immune modulation) in human studies published between 2020–2025 using rigorous inclusion criteria to address inconsistencies in findings. Methods We followed PRISMA/MOOSE guidelines, searching PubMed/MEDLINE, Embase, Web of Science, and Scopus. Included studies ( n = 20 observational; ≈20,000 cases) provided quantitative bacterial assessment (PCR, sequencing, or clinical periodontal/root canal diagnoses) and breast cancer outcome data. Risk of bias was assessed via Newcastle–Ottawa Scale. Random-effects meta-analysis pooled odds ratios (ORs) for incidence studies; subgroup and sensitivity analyses explored heterogeneity. Qualitative synthesis summarized progression and immune modulation findings. Results Meta-analysis of three studies showed no overall association (pooled OR = 1.00; 95% CI 0.62–1.58), but extreme heterogeneity (I 2 = 98%) reflected methodological disparities. A Greek case–control study reported elevated risk (OR = 1.79; 1.21–2.65), whereas a US cohort found no association (HR = 1.02; 0.94–1.11), and a claims-based analysis paradoxically suggested reduced risk (OR = 0.60; 0.57–0.63). F. nucleatum showed stronger associations in case–control studies, suggesting retrospective bias. Sensitivity analyses confirmed robustness (OR = 1.02; 0.66–1.57 after excluding lowest-quality study). Qualitative synthesis revealed inconsistent links, with some studies tying pathogens to advanced stages or cytokine alterations, while others reported null effects. Conclusion While epidemiologic data remain inconclusive and do not confirm a causal relationship between oral pathogens and breast cancer incidence (i.e., evidence remains inconclusive), translational evidence supports a role for F. nucleatum and P. gingivalis in tumor progression and immune evasion. These findings warrant future investigation into oral health as a modifiable factor in breast cancer progression.