Influence of inflammatory markers on the prognosis of patients with operable breast cancer

Abstract Introduction: To examine the relationship between neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), and prognostic nutritional index (PNI) and clinicopathological parameters in patients with breast cancer and determine their impact on prognosis in different molecular subtypes. Methods: We selected patients who underwent radical breast cancer surgery at the First Hospital of China Medical University from January 2012 to December 2018. Cut-off values for NLR, PLR, SII, LMR, and PNI were determined using the receiver operating characteristic curve. The relationship between inflammatory factors and clinicopathological parameters was analyzed using Pearson's chi-square and Fisher’s exact tests. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison. Factors impacting overall survival (OS) were determined using univariate and multivariate Cox regression models. The independent influencing factors were further used to perform the combined predictive models. Results: A total of 299 patients with breast cancer were enrolled. Age ( P = 0.007), tumor size ( P = 0.039), TNM stage ( P = 0.012), and axillary lymph node metastasis ( P < 0.0001) correlated with NLR. Multivariate analysis indicated that axillary lymph node metastasis (hazard ratio: 3.84, 95% confidence interval [CI]: 1.52-9.73, P = 0.005) (hazard ratio: 7.45, 95%CI: 1.24-44.72, P = 0.03) and NLR (hazard ratio: 2.73, 95%CI: 1.29-5.78, P = 0.009) (hazard ratio: 7.50,95%CI: 2.18-25.79, P = 0.001) were independent factors influencing OS. in the overall patients and hormone receptor (HR)+/ human epidermal growth factor receptor 2 (HER2)- subtype. PLR (hazard ratio: 2.97, 95%CI: 1.22-7.19, P = 0.016) (hazard ratio: 31.29, 95%CI: 3.04-321.7, P = 0.004) and SII (hazard ratio: 3.37, 95%CI: 1.29-8.84, P = 0.013) (hazard ratio: 8.87 95%CI: 1.06-74.15, P = 0.044) were relevant factors impacting OS in patients with HR+/HER2- and HR+/HER2+. Based on the independent influencing factors, we built the combined predictive models in the overall patients and patients with HR+/HER2-. Compared with other markers, combined predictive markers had the largest area under curve (AUC) in the overall patients (AUC=0.84, 95%CI: 0.78-0.90, P < 0.0001) and HR+/HER2- subtype (AUC=0.86, 95%CI: 0.78-0.94, P < 0.0001). Conclusion: NLR could be an independent prognostic indicator to predict OS in the overall patients and HR+/HER2- breast cancer.