Neutrophil-lymphocyte ratio reflects tumor infiltrating lymphocytes, tumor associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy

Abstract

Abstract Introduction The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumor microenvironment, tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aims to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods A cohort of breast cancer patients receiving NAC with subsequent was retrieved. Clinical data were reviewed. Histologic slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (post-chemotherapy) specimens were assessed for TILs and TAMs. Results Totally 146 patients were included. There was significant positive correlation between pre-chemotherapy and post-surgery NLR at a cutoff of 2.6 (median pre-chemotherapy NLR) (p<.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (p=.027) and excision (p=.021) and TAMs on excision (p=.049). NLR one-year post-surgery was associated with high tumor stage (p=.050) and low histologic grade (p=.008). TIL count was lower in NLR-high cases at nearly all time points, by histologic assessment and CD8 immunostaining (p<.050). In multivariate analysis, post-surgery NLR is an independent predictor for overall survival (OS) (HR=9.524, p<.001), breast cancer specific survival (BCSS) (HR=10.059, p=.001) and disease-free survival (DFS) (HR=2.824, p=.016). Conclusion The association between NLR with tumor necrosis, TAM and TIL illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.