Baseline neutrophil-lymphocyte ratio (NLR) predicts toxicity and survival in HR+/HER-2 breast cancer patients treated with CDK4/6 inhibitors

Abstract

The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been associated with prognosis in various malignancies. Its role in predicting toxicity and survival in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains unclear.

Methods

This retrospective cohort study included 2218 patients with HR+/HER2− metastatic breast cancer treated with palbociclib or ribociclib between 2017 and 2024, using data from Israel's largest health maintenance organization. We compared baseline NLR values between patients who developed grade 4 neutropenia (absolute neutrophil count <0.5 × 10⁹/L) and those with higher counts during the first three months of treatment. Additional comparisons were conducted using different neutropenia thresholds. We also assessed the association between baseline NLR (cut-off 2.5), progression-free survival (PFS), and treatment-related adverse events.

Results

Patients with grade 4 neutropenia had significantly higher baseline NLR values compared to those with higher neutrophil counts. The effect size was large in all comparisons. Patients with an NLR of ≥2.5 had a shorter median progression-free survival (PFS) than those with an NLR of <2.5. Hepatotoxicity was more frequently observed in patients with NLR <2.5, while the incidence of dermatologic adverse events was similar across groups.

Conclusions

Elevated baseline NLR is associated with an increased risk of severe neutropenia and shorter progression-free survival in patients treated with CDK4/6 inhibitors. These findings highlight a potential link between systemic inflammation and treatment outcomes, suggesting that NLR may be a valuable predictive biomarker in this setting.