Prognostic Significance Of Inflammatory Biomarkers In Patients With Breast Cancer Skeletal Metastases

Objective : To investigate whether the neutrophil/lymphocyte ratio(NLR),C-reactive protein/albumin ratio(CAR),and lymphocyte/monocyte ratio(LMR),these three systemic inflammatory response indexes,have a certain clinical predictive guiding role and research value in the prognosis of breast cancer patients with bone metastasis.Method: Patients who underwent postoperative review of breast cancer at the First Affiliated Hospital of Shihezi University School of Medicine between January 2009 and June 2020 were collected,and 212 patients with bone metastases from breast cancer were included in the study.The optimal cut-off value for each inflammatory biomarker was extracted from the receiver operating characteristic(ROC)curve.Patients were divided into the higher and lower value groups based on the cut-off values of NLR,CAR,and LMR.The correlation between NLR,CAR,LMR and clinicopathological characteristics were investigated.The differences in age,primary site,pathological type,histological grade,T stage,N stage,molecular classification,HER2,ER,PR,Ki-67,the number of bone metastases,and the visceral metastasis during follow-up were compared between the higher and lower NLR,CAR,and LMR groups.Cox univariate analysis was performed to examine prognostic factors,and multivariate regression analysis was used to identify independent prognostic factors.The differences in progression-free survival(PFS)and overall survival(OS)between the lower and higher NLR,CAR,and LMR groups were evaluated by Kaplan-Meier method.Results:1.The optimal cut-off values for NLR,CAR,and LMR were 2.48,0.34,and 3.43,respectively,and the corresponding area under the curve(AUC)were 0.648,0.534,and 0.625,respectively.Based on the optimal cut-off values,patients were divided into the higher and lower groups: lower NLR group(NLR<2.48)and higher NLR group(NLR≥2.48),lower CAR group(CAR<0.34)and higher CAR group(CAR≥0.34),lower LMR group(LMR<3.43)and higher LMR group(LMR≥3.43).Among them,90 patients were in the lower NLR group,and122 patients were in the higher NLR group;168 patients in the lower CAR group and 44 patients in the higher CAR group.There were 108 patients were in the lower LMR group and104 patients in the higher LMR group.2.The exploration of the relationship between NLR,CAR,and LMR and clinicopathological characteristics showed that CAR was significantly linked to the primary site and histological grade(P<0.001).However,there was no apparent association between NLR,LMR and clinicopathological features.3.Cox univariate analysis showed that patients with NLR≥2.48(P<0.001),CAR≥0.34(P=0.035),and LMR<3.43(P<0.001)had relatively poor PFS.OS was significantly shortened in patients with NLR≥2.48(P<0.001),CAR≥0.34(P=0.025),and LMR<3.43(P<0.001).4.Cox multivariate analysis showed that NLR≥2.48(HR 1.813,95%CI 1.071～3.067,P=0.027),LMR<3.43(HR 0.535,95%CI 0.323～0.884,P=0.015),the number of bone metastases 2-3(HR: 1.832,95%CI: 1.062-3.160,P=0.030),the number of bone metastases >3(HR: 2.129,95%CI: 1.036-4.375,P=0.004),radiotherapy for bone metastases(HR 0.447,95%CI 0.258～0.777,P=0.004),bisphosphonate therapy(HR 0.008,95%CI 0.002～0.029,P<0.001)and ER(+)(HR 0.503,95%CI 0.297～0.851,P=0.010)were independent prognostic factors for PFS.NLR≥2.48(HR 1.876,95%CI 1.107～3.179,P=0.019),CAR≥0.34(HR 1.684,95%CI 1.011～2.806,P=0.045),LMR<3.43(HR 0.568,95%CI 0.345～0.935,P=0.026),radiotherapy to bone metastases(HR 0.438,95%CI 0.252～0.762,P=0.003),bisphosphonate therapy(HR 0.008,95%CI 0.002～0.029,P<0.001),and ER(+)(HR 0.497,95%CI0.293～0.842,P=0.009)were independent prognostic factors for OS.5.Kaplan-Meier analysis showed that PFS was relatively shortened in patients with NLR≥2.48(P<0.001),CAR≥0.34(P=0.031),and LMR<3.43(P<0.001)groups;OS was significantly lower in NLR≥2.48(P<0.001),CAR≥0.34(P=0.022),and LMR<3.43(P<0.001)groups.Conclusion:1.Before systematic treatment,NLR and LMR were independent prognostic factors for PFS in patients with breast cancer bone metastasis,patients with NLR≥2.48 and LMR<3.43 indicated poor PFS.NLR,CAR and LMR were independent prognostic factors for OS,patients with NLR≥2.48,CAR≥0.34 and LMR<3.43 indicated worse OS.2.NLR,CAR,and LMR may serve as new indicators to predict the prognosis of breast cancer patients with bone metastases.