Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Abstract

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

Peripheral Blood Cell Ratios as Prognostic Indicators in a Neoadjuvant Chemotherapy-Treated Breast Cancer Cohort

“…NLR is one of the most commonly evaluated immunocyte ratio in breast cancer, and has often been shown to significantly associate with OS, DFS or pCR [ 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. However, few studies have evaluated applying more than one single immunocyte ratio in their cohorts.…”

“…The neutrophil-to-lymphocyte ratio (NLR) has emerged as a clinically-relevant measure of immune function in tumours, including breast cancer [ 8 , 9 , 10 , 11 ]. Ratios of peripheral blood cells have been correlated with clinically relevant outcomes, such as disease-free survival (DFS) and overall survival (OS) in breast cancer [ 12 , 13 ].…”

Prognostic Potential of Immune Inflammatory Biomarkers in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

“…A high NLR is generally associated with poor prognosis, as neutrophils have the potential to inhibit anti-tumor immunity by secreting a variety of inflammatory mediators and suppressing the cytotoxic activity of T cells [ 11 , 12 ]. However, the correlation between the biomarker and patient survival is much less consolidated in the neoadjuvant setting [ 13 , 14 , 15 ]. Many studies emphasize that a low pre-treatment NLR is associated with an increased pathologic complete response (pCR) rate [ 16 ], but this is particularly related to the tumor molecular subtype, and its correlation with long-term outcomes is still debated [ 8 , 15 , 17 ].…”

Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

“…Over 300 reports in PubMed and several systematic reviews and meta-analyses concern "neutrophil lymphocyte ratio, and breast cancer" [3][4][5][6]. More recent studies have reported a poorer prognosis and shorter survival times for breast cancer patients with higher NLRs [7][8][9][10][11]. The majority of these studies indicated that an NLR greater than the cutoff value of ~ 3 was associated with worse overall survival (OS) (hazard ratio (HR) 2.56, 95% confidence intervals CI = 1.96-3.35; P < 0.001) and disease-free survival (DFS) (HR 1.74, 95% CI = 1.47-2.07; P < 0.001), with a greater prognostic value for DFS in ER-negative and HER2-negative breast cancer [4].…”