Blood Cell Biomarker May Predict Anthracycline-Associated LV Dysfunction

Katherine Krive, DO, for Medscape

June 15, 2022

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Whereas an elevated neutrophil-to-lymphocyte ratio has been previously associated with increased risk for mortality in patients with cancer, the current study suggests it is also a predictor of risk for cardiotoxicity from anthracycline therapy in women with breast cancer.

  • The optimal neutrophil-to-lymphocyte ratio cut point for determining increased risk for impaired left ventricular (LV) function, as measured by echocardiographic global longitudinal strain (GLS), was 2.58, similar to the previously reported cut point of 3 for predicting breast cancer survival.

Why This Matters

  • Anthracyclines, especially doxorubicin, are a mainstay of treatment for breast cancer — the most prevalent cancer in women — yet their use can lead to irreversible LV dysfunction that is dose dependent.

  • Regular monitoring of neutrophil and lymphocyte counts could potentially contribute to risk stratification for anthracycline-associated LV dysfunction in women taking the drugs for breast cancer.

  • Such monitoring may be achieved with blood-count assays that are simpler to order and easier to obtain than the current monitoring method, measurement of LV contractile function using two-dimensional speckle-tracking echocardiography.

Study Design

  • The study prospectively enrolled 74 female patients (mean age 50) with breast cancer as participants in the Israel Cardio-Oncology Registry at the Tel Aviv Sourasky Medical Center from 2016 to 2021.

  • Participants were excluded if they were male, younger than 18, with an LV ejection fraction < 53%, had a history of cardiac disease or anthracycline or dexrazoxane therapy, or were missing documentation of white blood cell (WBC) counts or echocardiographic LV GLS data.

  • Patients were scheduled to receive doxorubicin to a cumulative dose of at least 180 mg/m2.

  • Echocardiography was performed before the start of treatment and after it concluded. Significant LV dysfunction was defined as at least a 10% reduction in LV GLS from baseline to the end of therapy.

  • Blood assays were performed and neutrophil-to-lymphocyte determined at both time points.

Key Results

  • Cardiac risk factors were observed up to 22% of patients; 18% of the total group were on cardioprotective medications including ACE inhibitors, angiotensin receptor blockers, and beta-blockers.

  • Some patients were also receiving monoclonal-antibody-based therapies, such as trastuzumab (Herceptin) in 22% and pertuzumab (Perjeta) in 19%. Additionally, 22% had undergone chest radiation.

  • Nearly all patients (99%) completed four cycles of doxorubicin treatment.

  • Median time from first doxorubicin treatment to the first follow-up evaluation of neutrophil-to-lymphocyte ratio was 44 days. On average, neutrophil-to-lymphocyte values had increased significantly (2.1 to 3.0; P < .001).

  • The changes in ratio were primarily due to loss of lymphocytes, whereas absolute neutrophil counts usually held steady.

  • The optimal neutrophil-to-lymphocyte ratio cut point for stratifying risk for LV functional deterioration by LV GLS was identified as 2.58 with a 79% sensitivity and 52% specificity.

  • Those with ratios of at least 2.58 were more than twice as likely to have a 10% or greater reduction in LV GLS compared with those with ratios in the lower range (50% and 20%, respectively, P = .009).

  • Using a multivariate binary logistic regression model, a neutrophil-to-lymphocyte ratio 2.58 or higher was associated with a fourfold increase in relative risk for LV GLS deterioration, odds ratio (OR) 4.63 (95% CI, 1.29 - 16.5, P = .02).

  • According to a second model, each 1-point elevation in the ratio predicted a 15% increment in risk for LV GLS deterioration, OR 1.15 (95% CI, 1.01 - 1.32, P = .046).


  • The study was single-center.

  • Its statistical power is reduced from the relatively small sample size, indicating a need for verification in larger studies.

  • The relatively short follow-up precluded evaluation of neutrophil-to-lymphocyte ratio as a predictor of reduced LV ejection fraction, cardiac morbidity, or all-cause mortality.


  • The senior author was the recipient of a grant from Pfizer Pharmaceuticals Israel in 2019 in support of the Israel Cardio-Oncology Registry.

  • The authors declare they have no conflicts of interest.

This is a summary of a preprint research study, "High neutrophil-to-lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline,"  written by researchers at the Israel Institute of Technology, Tel Aviv University, and Tel Aviv Sourasky Medical Center on, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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