Could Silent Inflammation Originating in Jawbone Cavitations Play a Role in Activating the CCL5/CCR5 Axis in Female Breast Cancer? A Diagnostic and Therapeutic Gap in Osteoimmunological Interactions

Joana Vasconcelos e Cruz,1,2 Sebastjan Perko,3 Cornelia Doebis,4 Florian Notter,5 Fabian Schick,5 Johann Lechner6 1Dental Materials, Egas Moniz School of Health & Science, Caparica, Portugal; 2Dental Materials, Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Caparica, Portugal; 3Maxillofacial Surgery, Klinika Maha Integrativna Medicina, Ljubljana, Slovenia; 4Immunology and Allergy, IMD-Berlin, Berlin,Germany; 5Maxillofacial Surgery, Clinic for Integrative Dentistry, Munich, Germany; 6Clinic for Integrative Dentistry, Munich, GermanyCorrespondence: Johann Lechner, Clinic for Integrative Dentistry, Gruenwalder Str. 10A, Munich, 81547, Germany, Tel +49 89 697 0129, Fax +49 89 692 5830, Email [email protected]: Breast cancer (BC) is one of the leading causes of cancer mortality worldwide. The chemokine CCL5 and its receptor CCR5 have been demonstrated to be associated with tumour progression, immune evasion, and metastasis.Objective: Recent evidence indicates that chronic inflammatory conditions in the jawbone, specifically fatty degenerative osteonecrosis of the jaw (FDOJ), may serve as a continuous source of CCL5 overexpression, potentially influencing BC development.Methods: This multicentre study, conducted in Germany, Portugal and Slovenia, investigated the correlation between FDOJ-related CCL5 expression and BC. Patients undergoing surgical removal of FDOJ areas were examined using advanced imaging (trans alveolar ultrasonography) and multiplex cytokine analysis to detect bone marrow defects and measure CCL5 levels.Results: The results demonstrated a marked increase in CCL5 expression in FDOJ samples in comparison to healthy jawbone tissue.Discussion: Statistical analysis revealed a strong correlation between FDOJ and elevated CCL5, thereby supporting the hypothesis that jawbone inflammation may activate the CCL5/CCR5 axis in BC patients. This finding suggests that FDOJ may represent an underrecognized inflammatory comorbidity that contributes to BC progression.Conclusion: The study under discussion highlights a hitherto unidentified osteoimmune mechanism that links inflammation of the jawbone to cancer pathways. It also emphasizes the potential benefit of targeted surgical interventions such as “Jawbone Detox®” in reducing chronic CCL5 levels. Such approaches have the potential to offer novel preventive and therapeutic options for patients diagnosed with BC. Further clinical studies are required to confirm the effects of FDOJ treatment on immune function and BC outcomes. Keywords: breast cancer, CCL5, CCR5, FDOJ, trans alveolar ultrasonography, TAU