Association of tumor-infiltrating lymphocytes and proinflammatory biomarkers with breast cancer molecular subtypes: analysis of the MEND study.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) and proinflammatory biomarkers shape breast cancer (BC) progression and outcomes. We estimated the association between TILs and BC subtypes in Nigerian women and, in exploratory analyses, evaluated relationships between serum biomarkers (IL-6, IL-8, IL-1β, TNF-α, and leptin), TILs and BC subtypes. METHODS: TILs were quantified on H&E-stained tumors from 436 treatment-naïve Nigerian BC patients, serum biomarkers (n = 109) were profiled by Meso Scale Discovery immunoassays. TILs and proinflammatory biomarkers were assessed across BC subtypes using descriptive analyses and multinomial logistic regression; cytokine ratios were also explored to characterize TNF-α dominance. RESULTS: Median age was 49, and subtypes were triple-negative (TNBC, 43%), luminal A (31%), luminal B (12%), and HER2-enriched (15%). Median TIL percentage was 10.0 (Q1, Q3: 4.0, 21.0), with 49% of patients classified as low TIL (< 10%), 41% as intermediate (10- < 40%) and 10% as high (≥ 40%). Compared to low TILs, medium (OR 1.94, 95% CI 1.11-3.38, p = 0.020) and high TILs (OR 2.65, 95% CI 1.00-6.99, p = 0.049) were associated with higher odds of TNBC vs. ER+ after demographic and clinical adjustments. TNF-α correlated with TILs (ρ: 0.21; p = 0.026) and higher TNF-α:IL-1β (OR 4.16, 95% CI 1.35-12.84) and TNF-α:IL-8 (OR 3.81, 95% CI 1.29-11.23) ratios were associated with TNBC but not HER2 (vs. ER+); individual biomarkers were not associated with subtypes. CONCLUSION: Elevated TILs and TNF-α-dominant profiles are associated with TNBC (vs. ER+) in Nigerian women, highlighting potential immunotherapy relevance in Nigerian TNBC cases and a suggestive prognostic/therapeutic role for TNF-α.

Duke Scholars

Author Tomi Akinyemiju Population Health Sciences

Author April Deveaux Population Health Sciences

Author Allison Haberstroh Sandler Hall Pathology