Lactate Dehydrogenase as a Potential Mediator Between Immature Granulocytes and Tumor Burden in Breast Cancer

Background: Chronic inflammation and metabolic dysregulation contribute to breast cancer initiation and progression. Immature granulocytes (IG) and lactate dehydrogenase (LDH) reflect systemic inflammation and metabolic activity, respectively, but their interplay in tumor growth remains unclear. Objective: To investigate the associations among IG, LDH, and breast tumor size, and to evaluate whether LDH mediates the relationship between IG and tumor burden. Methods: A total of 778 breast cancer patients undergoing primary surgery were included. Peripheral blood IG counts and LDH levels were measured within two weeks preoperatively, and tumor size was obtained from postoperative pathology reports. Associations were assessed using SHAP feature importance analysis, univariate and multivariate linear regression, weighted linear regression, and subgroup analyses. Mediation analysis evaluated the potential mediating role of LDH. Results: In weighted and multivariable linear regression analyses, both IG count and LDH levels were significantly positively associated with tumor size. After full adjustment, IG remained an independent predictor of tumor size (β = 6.09, P = 0.01), and LDH showed a similar association (β = 0.01, P = 0.014). IG count was also strongly correlated with LDH levels (β = 241.52, 95% CI: 86.97-396.06, P < 0.01). Mediation analysis indicated that LDH partially mediated the IG-tumor size association, accounting for 9.86% of the total effect. Subgroup analysis suggested that the relationship between IG and tumor size is modulated by hypertension. Conclusion: These findings suggest a potential interplay between systemic inflammation and tumor metabolism in breast cancer progression. IG and LDH may serve as accessible biomarkers associated with tumor burden and could assist in risk stratification and clinical decision-making. Multicenter prospective studies are required to validate these associations and further elucidate the underlying biological mechanisms.