Prognostic role for derived neutrophil-to-lymphocyte ratio in early breast cancer

Abstract

Background: Inflammation is a hallmark of cancer. Elevated markers of host inflammation have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil‐to‐lymphocyte ratio (dNLR) in subgroups of women with early breast cancer. Methods: This was a retrospective analysis of women with early breast cancer included in the GEICAM/9906 trial, a randomized phase III study of adjuvant FEC compared to FEC‐paclitaxel (FEC‐P) in breast cancer patients with axillary involvement. dNLR was calculated as the ratio of neutrophils divided by the difference between total leukocytes and neutrophils measured in peripheral blood before the start of chemotherapy. The primary objective was disease free survival (DFS) and overall survival (OS) was a secondary endpoint. Univariable Cox regression was used to explore the prognostic and predictive value of dNLR (explored as median cutoff and grouped in quartiles). Subgroups by PAM50 subtype and hormonal receptor expression were subsequently analyzed. Results: The current analysis comprised 1243 patients from 65 Spanish sites with a median follow‐up of 10 years. Median age was 50 years (range 23‐76), 66% of patients had available PAM50 subtype determination, of which 22% of the tumors were Luminal A, 21% Luminal B, 14% Her2‐enriched, 6% Basal‐like, and 3% Normal‐like. ER+/PgR+ and ER‐/PgR‐ subtypes comprised 47% and 13% of evaluable tumors, respectively. Median dNLR was 1.35 (IQR 1.08 ‐ 1.71). For Her2‐enriched patients by PAM50, a dNLR > median was significantly associated with worse DFS, p = 0.03 (HR: 1.63; 95%CI: 1.04 ‐ 2.54). For non‐luminal patients by PAM50, a dNLR > median and a high dNLR explored by quartiles were associated with worse DFS (p = 0.02 and p = 0.03, respectively). For patients with ER‐/PgR‐ tumors, a high dNLR grouped in quartiles was associated with worse DFS and OS (p < 0.001 and p = 0.007, respectively). Conclusions: dNLR is associated with worse DFS in women with Her2‐enriched and non‐luminal intrinsic subtypes defined by PAM50 multigene expression assay. High dNLR is also associated with worse DFS and OS in women with ER‐/PgR‐ tumors (IHC). Further studies are warranted to confirm these findings.