The prognostic role of pretreatment neutrophil-to-lymphocyte ratio in a multiethnic cohort of breast cancer patients

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation linked to poor outcomes in several solid tumor malignancies, including breast cancer. Prior studies have shown that its prognostic significance in breast cancer differs by molecular subtype; however, these studies have rarely accounted for racial variation in baseline NLR values, which may affect the interpretation of threshold-based analyses. This study evaluates the prognostic value of pretreatment NLR in breast cancer and whether associations between NLR and survival outcomes differ by race and tumor subtype. Methods: We conducted a retrospective analysis of 754 patients from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. Eligible patients had an NLR measurement ≤1 year prior to treatment initiation. NLR was analyzed as both continuous and binary variables, using a cohort-wide median cutoff (2.07) and race-specific cutoffs (3.11 for White and 2.56 for Black patients). Outcomes included recurrence-free survival (RFS), overall survival (OS), breast cancer-specific survival (BCSS), and other-cause (OC) mortality. Cox and competing risk regression models were used to estimate the associations between NLR and survival outcomes, adjusting for demographic and clinical covariates. Results: Among 754 patients (mean age at diagnosis 55.9 years), 383 were Black, 308 were White, and 63 were categorized as Other. The median pretreatment NLR was lower in Black patients (1.78, IQR 1.30-2.61) compared to White (2.38, IQR 1.69-3.11) and Other racial patients (2.06, IQR 1.41-2.89). In adjusted analyses, each doubling of NLR was associated with worse RFS (adjusted hazard ratio [aHR] 1.24, 95% CI 1.02-1.52), OS (aHR 1.20, 95% CI 0.98-1.48), and OC mortality (aSHR 1.42, 95% CI 1.07-1.89). When modeled as a binary variable, high NLR (≥2.07) was associated only with higher OC mortality (adjusted sub-distribution hazard ratio [aSHR] 2.11, 95% CI 1.11-4.02). Stratified analyses showed that the association between NLR and survival outcomes was most pronounced in HER2-negative and hormone receptor-positive tumors, whereas no significant associations were observed in hormone receptor-negative tumors. When using race-specific thresholds, high NLR (≥2.56) was significantly associated with worse RFS (aHR 2.02, 95% CI 1.27-3.21), OS (aHR 1.93, 95% CI 1.15-3.21), and BCSS (aSHR 2.31, 95% CI 1.12-4.78) in Black patients, but not in White patients. Conclusion: Our study demonstrates that pretreatment NLR may be used as a prognostic marker for breast cancer outcomes, but its predictive value varies by race and tumor subtype. Baseline racial differences in NLR underscore the need for race-specific thresholds. Larger, diverse studies are needed to validate these findings and clarify underlying biological mechanisms.