Correlation of neutrophil-to-lymphocyte ratio and stromal tumor infiltrating lymphocytes across early breast cancer subtypes.

Abstract

e12558 Background: The tumor microenvironment plays a key role in the treatment response and prognosis of breast cancer (BC) patients, but the integrity of the peripheral immune system is also relevant. Understanding the biological correlation of immune-related prognostic factors, such as neutrophil-to-lymphocyte ratio (NLR) and stromal tumor infiltrating lymphocytes (sTIL), is necessary to improve its clinical applicability and the possible generation of more complex biomarkers that can direct treatment. Methods: Observational and single-center cohort of 1006 early BC patients (2009-2020). Pre-treatment NLR in peripheral blood and sTIL at diagnostic biopsy were determined. The correlation between NLR and sTIL (Spearman's Rho) overall and by subtypes, as well as its prognostic value for overall (OS) or disease-free survival (DFS) by Cox regression were evaluated. Results: NLR could be determined in 965 (96%) patients; in536 (53%) patients both NLR and sTIL were available. No statistical differences in baseline characteristics between both cohorts were found. Median age: 50 (range: 24-89); 93% infiltrating ductal carcinoma; 39.4% grade 3; 42.2% stage III; subtypes: hormone receptor (HR)+/HER2- (78.2%), HER2+/HR(+/-)(9.9%), triple negative breast cancer (TNBC) (11.9%); 70.5% treated with neoadjuvant chemotherapy. Median sTIL was 5% (SD: 16.2) with higher values in grade 3 (p < 0.001), HR- (p < 0.001) and HER2+ (p = 0.001). The median NLR was 1.95 (SD: 1.20), with no differences by subtype. There was no overall relationship between NLR and sTIL (ρ:0.32, p = 0.456). Correlation was also ruled out for each molecular subtype: HR+/HER2- (ρ:0.05, p = 0.301), HER2+/HR(+/-) (ρ:0.16, p = 0.251) and TNBC (ρ:0.21, p = 0.104). In a univariate predictive model for survival (N = 965), NLR showed prognostic value for DFS (HR 0.96, 95%CI: 0.80-1.17, p = 0.711) or OS (HR 1.02, 95%CI: 0.85-1.23, p = 0.798), neither in the whole group nor in the analysis by immunochemical subtypes. Conclusions: No correlation was observed between two of the most relevant biomarkers of immune activation in the tumor (sTIL) and peripheral (NLR) compartment in a series of early BC patients. NLR was not predictor of survival in our cohort. The absence of relationship between sTIL and NLR could suggest differences in the immune response in both compartments or else the need to find more accurate peripheral immune activation markers.