Neutrophil-to-lymphocyte ratio as a predictor of survival in patients with triple-negative breast cancer
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Peripheral blood lymphopenia and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with poor outcomes in various malignancies. However, existing literature has largely focused on baseline parameters. The aim of this study is to assess the impact of radiation therapy (RT) and chemotherapy on absolute lymphocyte counts (ALC) and NLR in relation to survival outcomes in patients with triple-negative breast cancer (TNBC).
A retrospective analysis was performed on 126 patients with TNBC treated at Washington University between 2005 and 2010. Cox proportional hazard model with time-varying covariates was applied to estimate the effect of time-varying ALC and NLR separately on overall survival (OS) and disease-free survival (DFS).
All patients received RT and 112 patients received either neoadjuvant chemotherapy or adjuvant chemotherapy, or both. Patients deceased had lower ALC and higher NLR compared to patients alive throughout the treatment course, even 1 year after treatment completion (ALC, 1 vs. 1.3, P = 0.03 and NLR, 3.9 vs. 2.6, P = 0.03). High ALC was associated with superior OS on both continuous and binary scales (cutoff of 1 K/ul) (HR 0.14; 95% CI 0.05–0.34; P < 0.001 and HR 0.28; 95% CI 0.13–0.61; P = 0.01, respectively). Additionally, high NLR was weakly associated with inferior OS on continuous scales (HR 1.1; 95% CI 1.06–1.15; P < 0.001).
Post-treatment lymphopenia and NLR elevation can persist until 1 year after treatment completion. Both portend shorter survival for patients with TNBC. Our data support the use of ALC and NLR to identify high risk patients who may benefit from clinical trials rather than standard of care therapy.
KeywordsNeutrophil-to-lymphocyte ratio (NLR) Triple-negative breast cancer (TNBC) Overall survival (OS)
Absolute lymphocyte count
Absolute neutrophil count
Cytotoxic T-lymphocyte-associated protein 4
Derived neutrophil-to-lymphocyte ratio
Electronic patient record
Human epidermal growth factor receptor 2
Metastatic breast cancer
- NK cell
Natural killer cell
Programmed cell death protein 1
Programmed death ligand 1
Triple-negative breast cancer
Treatment related lymphopenia
White blood count
We thank Mr. Ashwin Govindan for database assistance.
DAP was involved in data collection and the writing, revision and approval of the manuscript. JX was involved in statistical data analysis and the writing, revision and approval of the manuscript. JL was involved in statistical data analysis and the writing, revision and approval of the manuscript. BH was involved in the writing, revision and approval of the manuscript. ST was involved in the writing, revision and approval of the manuscript. CXM was involved in study design and the writing, revision and approval of the manuscript. JLC was involved in study design, study supervision and the writing, revision and approval of the manuscript.
The authors received no specific funding for this work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Consent for publication
All authors listed above have reviewed and verified the manuscript for accuracy. All authors have consented to be an author and publish the manuscript.
This retrospective study protocol was approved by Washington University Institutional Review Board (IRB) (Reference #: 201406126). Upon approval, Washington University agreed to follow the Declaration of Helsinki, Good Clinical Practice guidelines, and the applicable parts of the United States Code of Federal Regulations.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was not required for this retrospective analysis.
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