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Neutrophil-to-lymphocyte ratio as a predictor of survival in patients with triple-negative breast cancer

  • Dilan A. Patel
  • Jing Xi
  • Jingqin Luo
  • Bilal Hassan
  • Shana Thomas
  • Cynthia X. Ma
  • Jian L. CampianEmail author
Clinical trial
  • 63 Downloads

Abstract

Purpose

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).

Methods

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).

Results

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).

Conclusions

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.

Keywords

Neutrophil-to-lymphocyte ratio (NLR) Triple-negative breast cancer (TNBC) Overall survival (OS) 

Abbreviations

ALC

Absolute lymphocyte count

ANC

Absolute neutrophil count

CI

Confidence interval

CTLA-4

Cytotoxic T-lymphocyte-associated protein 4

DFS

Disease-free survival

dNLR

Derived neutrophil-to-lymphocyte ratio

EPR

Electronic patient record

ER

Estrogen receptor

HER2

Human epidermal growth factor receptor 2

HR

Hazard ratio

MBC

Metastatic breast cancer

NK cell

Natural killer cell

NLR

Neutrophil-to-lymphocyte ratio

OS

Overall survival

PD-1

Programmed cell death protein 1

PD-L1

Programmed death ligand 1

PR

Progesterone receptor

RT

Radiation therapy

TNBC

Triple-negative breast cancer

TRL

Treatment related lymphopenia

WBC

White blood count

IL-7

Interleukin 7

IL-15

Interleukin 15

Notes

Acknowledgements

We thank Mr. Ashwin Govindan for database assistance.

Author contributions

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.

Funding

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.

Ethical approval

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

Informed consent was not required for this retrospective analysis.

Supplementary material

10549_2018_5106_MOESM1_ESM.docx (36 kb)
Supplementary material 1 (DOCX 36 KB)
10549_2018_5106_MOESM2_ESM.pdf (50 kb)
Kaplan-Meier curve to compare overall survival (OS) between patients with baseline (BL) neutrophil-to-lymphocyte ratio (NLR) equal or more than 3 and those with baseline NLR less than 3. Abbreviations: BL, baseline; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; HR, hazard ratio. Supplementary material 2 (PDF 49 KB)
10549_2018_5106_MOESM3_ESM.pdf (45 kb)
Kaplan-Meier curve to compare disease-free survival (DFS) between patients with baseline (BL) neutrophil-to-lymphocyte ratio (NLR) equal or more than 3 and those with baseline NLR less than 3. Abbreviations: BL, baseline; NLR, neutrophil-to-lymphocyte ratio; DFS, disease-free survival; HR, hazard ratio. Supplementary material 3 (PDF 45 KB)
10549_2018_5106_MOESM4_ESM.pdf (45 kb)
Kaplan-Meier curve to compare overall survival (OS) between patients with baseline (BL) absolute lymphocyte count (ALC) equal or more than 1 and those with baseline ALC less than 1. Abbreviations: BL, baseline; ALC, absolute lymphocyte counts; OS, overall survival; HR, hazard ratio. Supplementary material 4 (PDF 45 KB)
10549_2018_5106_MOESM5_ESM.pdf (44 kb)
Kaplan-Meier curve to compare disease-free survival (DFS) between patients with baseline (BL) absolute lymphocyte count (ALC) equal or more than 1 and those with baseline ALC less than 1. Abbreviations: BL, baseline; ALC, absolute lymphocyte count; DFS, disease-free survival; HR, hazard ratio. Supplementary material 5 (PDF 44 KB)
10549_2018_5106_MOESM6_ESM.pdf (47 kb)
Kaplan-Meier curve to compare overall survival (OS) among clinical stage I, stage II and stage III triple-negative breast cancer patients. Supplementary material 6 (PDF 47 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Washington University School of MedicineSt. LouisUSA
  2. 2.Vanderbilt University School of MedicineNashvilleUSA
  3. 3.St. Luke’s HospitalSt. LouisUSA
  4. 4.Division of OncologyWashington University School of MedicineSt. LouisUSA

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