Evaluation of the effect of periodontitis on breast cancer metastasis

Periodontitis is a chronic and multifactorial disease characterized by progressive destruction of periodontal tissues. Current literature suggests that periodontitis is not merely a localized oral infection, but also increases systemic inflammatory burden and may be associated with various systemic diseases, including cancer. Breast cancer is the most common malignancy among women, and metastasis remains the main cause of mortality. Proinflammatory cytokines and chemokines play a crucial role in the tumor microenvironment, and these biomarkers may influence the metastatic process through shared mechanisms with periodontitis. The present study aimed to evaluate the relationship between periodontitis and breast cancer metastasis. This study was conducted at the Department of Periodontology, Faculty of Dentistry, Selçuk University. A total of 71 breast cancer patients (with or without metastasis) diagnosed at the Department of Medical Oncology, together with 38 systemically healthy controls, were included. All participants underwent comprehensive periodontal examination, and clinical parameters including probing depth (PD), clinical attachment loss (CAL), plaque index (PI), gingival index (GI), bleeding on probing (BOP), periodontal epithelial surface area (PESA), periodontal inflamed surface area (PISA), and the ratio of BOP to PD ≥4 mm (BOP/PD4+) were recorded. In addition, unstimulated saliva and serum samples collected prior to periodontal examination were analyzed for IL-1β, IL-6, IL-10, MCP-1, RANTES, and ENA-78 levels using the enzyme-linked immunosorbent assay (ELISA). Breast cancer patients were stratified into subgroups according to lymph node metastasis status [LN(–) vs. LN(+)] and periodontal status [gingivitis/mild–moderate periodontitis (stage I–II) vs. severe periodontitis (stage III–IV)]. The mean age of breast cancer patients was significantly higher compared to healthy controls (p<0.001), whereas no significant differences were observed in body mass index (p>0.05). Regarding periodontal parameters, PD, CAL, GI, and PI were significantly higher in the breast cancer group compared with healthy controls (p<0.005). Biochemical analyses revealed that salivary IL-1β levels were significantly elevated in breast cancer patients, while serum IL-6, IL-10, MCP-1, and ENA-78 levels were significantly lower than those in healthy controls (p<0.001). Conversely, RANTES levels were significantly higher in both saliva and serum samples of breast cancer patients compared with controls (p<0.001). In subgroup analyses, the BOP/PD4+ ratio was significantly higher in the LN(+) severe periodontitis (stage III–IV) group compared with the LN(–) group (p<0.001). This significance was not observed in gingivitis or mild–moderate periodontitis groups (p>0.05). Multivariate logistic regression analysis identified BOP/PD4+ as an independent predictor of lymph node metastasis with high sensitivity (OR≈1.078, AUC=0.805). In conclusion, our findings indicate that periodontitis may not be confined to local tissue destruction but could interact with systemic immune responses, potentially influencing metastatic progression in breast cancer patients. In particular, the presence of BOP in periodontal pockets ≥4 mm emerged as a strong risk indicator for metastasis, suggesting that active periodontal inflammation in severe disease may contribute to systemic dissemination and metastatic processes. These findings highlight the importance of considering the periodontal–oncologic interplay in clinical management strategies and underscore the need to integrate periodontal health into comprehensive cancer care.