Prognostic Value of Pretreatment Lymphocyte-to-Monocyte Ratio and Development of a Nomogram in Breast Cancer Patients

Abstract

Purpose: The objective of this study was to explore the prognostic significance of pretreatment hematologic parameters in predicting disease-free survival (DFS) of breast cancer patients.

Materials and methods: The medical records of 440 breast cancer patients in Shandong Cancer Hospital and Institute from 2003 to 2013 were analyzed retrospectively. Through the results of blood routine before treatment, the absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), and absolute platelet count (APC) in peripheral blood were collected. The lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-monocyte ratio (NMR) were calculated. Cox proportional hazard model was used for univariate and multivariate analysis. The DFS was compared using Kaplan-Meier method. The prognostic nomogram of patients with breast cancer was developed.

Results: The median DFS for all patients was 64.10 months. Univariate analysis showed that the DFS was associated with surgical approach, TNM stage, molecular subtype, neoadjuvant chemotherapy, radiotherapy, and LMR (p < 0.05). TNM stage, molecular subtype, and LMR were independent prognostic factors of breast cancer in multivariate analysis (p < 0.05). According to the Kaplan-Meier survival curve analysis, patients with higher LMR (≥4.85) were associated with longer median DFS (median DFS, 85.83 vs. 60.90, p < 0.001). The proposed nomogram that incorporated LMR, TNM stage, and molecular subtype got a concordance index (c-index) of 0.69 in predicting 5-year DFS.

Conclusion: In breast cancer patients, higher LMR was associated with longer median DFS and the nomogram including LMR, TNM stage, and molecular subtype could accurately predict the prolonged 5-year DFS of breast cancer patients.

Keywords: breast cancer; disease-free survival (DFS); hematologic parameters; lymphocyte-to-monocyte ratio (LMR); nomogram.

Figure 1

Kaplan–Meier estimates of the DFS of breast cancer patients according to the LMR level in overall patients.

Figure 2

Nomogram for the prediction of DFS. (A) A nomogram for predicting the 5-year DFS for 440 patients with breast cancer (molecular subtype: 1 = luminal A, 2 = luminal B, 3 = HER-2, 4 = TNBC). To calculate the 5-year DFS for a specific patient, locate patient’s pretreatment LMR and draw a line straight upward to the Points axis to determine the score associated to that LMR. Repeat the process for TNM stage and molecular subtype, sum the scores, and locate this sum on the Total Points axis. Then, draw a line straight down to the corresponding “5-year DFS” axis to find the predicted 5-year DFS. (B) Calibration curves for 5-year DFS using nomograms with TNM stage, molecular subtype, and pretreatment LMR are shown. The x-axis is nomogram predicted probability of survival and y-axis is actual survival. The bootstrapping method was used for the internal validation of the nomogram. The gray line indicates perfect calibration.