The prognostic value of neutrophil-to-lymphocyte ratio in de novo stage IV breast cancer: a retrospective cohort study.

Background:The presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. And the majority of studies on breast cancer (BC) analyzed patients with early-stage. Fewer studies focused on metastatic BC (MBC). De novo stage IV BC with no prior treatment is more suitable for analyzing prognostic factors. Herein, we examined the prognostic value of baseline NLR in de novo stage IV BC patients. Methods:We retrospectively screened the medical records of female patients who were diagnosed with de novo stage IV BC at Peking University Cancer Hospital between January 2011 and December 2020. All patients were followed up by telephone every 6 months. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of NLR for progression-free survival (PFS). Peripheral blood lymphocyte subsets and tumor infiltrating lymphocytes (TILs) were analyzed by flow cytometry and immunohistochemistry, respectively. Correlations of PFS and overall survival (OS) with NLR and other clinicopathological factors were evaluated using Kaplan-Meier method and Cox regression analyses. Results:A total of 128 patients between January 2011 and December 2020 were enrolled. 70 (54.7%) cases were hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, 79 (61.7%) patients had visceral metastasis and 67 (52.3%) patients had more than 2 metastatic sites. The cutoff values of NLR were 2.9, optimized by ROC curve analysis. Totals of 77 and 51 patients were assigned to the NLR-low (≤2.9) and NLR-high (>2.9) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median PFS (14.8 vs. 7.2 months; hazard ratio =1.791; P=0.003). The OS showed no significant difference (64.1 vs. 56.0 months, P=0.980). The patients with NLR-low had a higher level of peripheral CD3+ T cells (P=0.028) and a lower level of peripheral CD4+CD25+ regulatory T (Treg) cells (P=0.041). Patient samples with NLR-low also demonstrated higher levels of TILs than those with NLR-high (P=0.025). Conclusions:The baseline NLR-high is associated with adverse PFS in patients with de novo stage IV BC. The NLR-high status may indicate immune suppression status, which can help identify patients with unfavorable prognosis and assist with physicians' treatment decision.