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

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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.

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Data availability

All data and material are available upon request.

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

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Acknowledgements

We thank Mr. Ashwin Govindan for database assistance.

Funding

The authors received no specific funding for this work.

Author information

Author notes

  1. Dilan A. Patel and Jing Xi are Co-first authors.

Authors and Affiliations

  1. Washington University School of Medicine, St. Louis, MO, 63110, USA

    Dilan A. Patel, Jing Xi, Jingqin Luo, Bilal Hassan, Shana Thomas, Cynthia X. Ma & Jian L. Campian

  2. Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Dilan A. Patel

  3. St. Luke’s Hospital, St. Louis, MO, 63017, USA

    Jing Xi

  4. Division of Oncology, Washington University School of Medicine, Campus Box 8056, 660 South Euclid Ave, St. Louis, MO, 63110, USA

    Jian L. Campian

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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.

Corresponding author

Correspondence to Jian L. Campian.

Ethics declarations

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 36 KB)

10549_2018_5106_MOESM2_ESM.pdf

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

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

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

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

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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Patel, D.A., Xi, J., Luo, J. et al. Neutrophil-to-lymphocyte ratio as a predictor of survival in patients with triple-negative breast cancer. Breast Cancer Res Treat 174, 443–452 (2019). https://doi.org/10.1007/s10549-018-05106-7

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