High neutrophil‐to‐lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline

Abstract

Background: Cardiotoxicity, de ned mainly as left ventricle (LV) dysfunction, is a signi cant side effect of anthracyclines (ANT) therapy. The need for an early simple marker to identify patients at risk is crucial.High Neutrophil-to-Lymphocyte Ratio (NLR) has been associated with poor prognosis in cancer patients, however, its role as a predictor for cardiotoxicity development is unknown.Objective: We aimed to evaluate whether elevated NLR, following ANT exposure, plays a predictive role in the development of cardiotoxicity as de ned by LV global longitudinal strain (LV GLS) relative reduction (≥10%).Methods and results: Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). A total of 74 female patients with breast cancer, scheduled for ANT therapy were included. NLR levels were assessed at baseline (T1) and during ANT therapy (T2). All patients underwent serial echocardiography at baseline (T1) and after the completion of ANT therapy (T3). NLR≥ 2.58 was found to be the optimal predictive cut-off for LV GLS deterioration. A relative LV GLS reduction ≥10% was signi cantly more common among patients with high NLR (50% vs. 20%, p=0.009). NLR ≥ 2.58 increases the risk for LV GLS reduction by 4-fold (OR 4.63,, p = 0.02), with each increase of 1-point NLR adding an additional 15% risk (OR 1.15, 95%CI 1.01-1.32, p = 0.046).Conclusions: Our study provides novel data that high NLR levels, following ANT exposure, have an independent association with the development of LV dysfunction. Routine surveillance of NLR may be an effective means of risk-stratifying.

High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy

“…Although, sensitivity and specificity of NLR for prediction of CTR-CVT in our study cohort were not ideal, they increased the diagnostic validity of the established parameters like NT-proBNP and high-sensitive troponin, highlighting the additional benefit of this economically biomarker. Also, an AUC of 0.63 appears moderate for the prediction of overall CTR-CVT, but compared to other studies, investigating the association of NLR with cardiotoxicity under anti-cancer treatment similar values for AUC is reported [ 33 ]. The same applies to studies examining the association of NLR with mortality or myocardial injury in other non-cancer collectives [ 39 – 41 ].…”

“…These results further confirm the association of NLR with CTR-CVT as reported before in other studies. In patients with breast cancer under anthracycline therapy, NLR was associated with deterioration of left ventricular global longitudinal strain (GLS) [ 33 ]. High NLR values were also observed in patients with ICI-related myocarditis and arrhythmia [ 32 , 42 ].…”

“…This is not exclusively observed in patients under ICI therapy and therefore not specific for prediction of CTR-CVT in ICI recipients. Previous studies, however, have concluded that NLR may predict cardiotoxicity in breast cancer patients under anthracycline treatment [ 33 ]. In addition, NLR is associated with mortality in cancer patients independent of anti-cancer treatment [ 53 – 55 ].…”

“…Cancer patients with ICI-related CTR-CVT showed higher NLR values, but no specific analysis of its predictive capacity for patients with pre-existing cardiovascular disease was performed [ 32 ]. In patients with breast cancer under anthracycline therapy, high NLR values were associated with early signs of CTR-CVT [ 33 ]. Increased NLR was associated with major adverse cardiac events (MACE) in patients with ICI myocarditis [ 34 ].…”

New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review

“…Recently, novel studies have focused on investigating whether elevated neutrophil-to-lymphocyte ratio (NLR) may have a predictive role in the onset and development of cardiotoxicity in breast cancer patients treated with anthracyclines. Baruch et al, 2023 [ 288 ], were the first to evaluate the role of NLR in predicting anthracycline-induced cardiotoxicity using LV GLS and revealed that patients with NLR ≥ 2.58, which was set as the cut-off value, had twice as high risk for LV GLS reduction by ≥10% (50% vs. 20%, p = 0.009) in response to anthracycline-based chemotherapy. It is interesting to note that the change in the NLR ratio was attributed to the lower levels of absolute lymphocyte counts during treatment, T2, (1.1 [0.8–1.5]; p < 0.001) compared to baseline, T1 (1.8 [1.5–2.3]).…”