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Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy

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Abstract

Purpose

Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer.

Patients and methods

This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis.

Results

The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08–1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR.

Conclusion

Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer.

Trial registration

EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7–11, 2016, Copenhagen, Denmark (oral presentation).

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Acknowledgements

The authors thank all investigators, trial coordinators, and the GEICAM staff for their hard work and all patients and their families for participation in the GEICAM/9906 study.

Funding

No specific funding was obtained for this study.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, St. Claraspital, Basel, Switzerland

    A. J. Templeton

  2. Faculty of Medicine, University of Basel, Basel, Switzerland

    A. J. Templeton

  3. Hospital Universitario de Elche, Elche, Spain

    Á. Rodríguez-Lescure

  4. GEICAM (Spanish Breast Cancer Group), Madrid, Spain

    Á. Rodríguez-Lescure, A. Ruíz, E. Alba, L. Calvo, M. Ruíz-Borrego, A. Santaballa, C. A. Rodríguez, C. Crespo, M. Ramos, J. M. Gracia-Marco, A. Lluch, I. Álvarez, M. I. Casas, M. Sánchez-Aragó, R. Caballero, E. Carrasco, M. Martin & A. Ocaña

  5. Instituto Valenciano de Oncología, Valencia, Spain

    A. Ruíz

  6. Hospital Virgen de la Victoria, Málaga, Spain

    E. Alba

  7. Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain

    E. Alba, A. Lluch & M. Martin

  8. Complejo Hospitalario Juan Canalejo, A Coruña, Spain

    L. Calvo

  9. Hospital Univ. Virgen del Rocío, Seville, Spain

    M. Ruíz-Borrego

  10. Hospital Universitario La Fe, Valencia, Spain

    A. Santaballa

  11. Hospital Clínico Universitario de Salamanca, Salamanca (IBSAL), Salamanca, Spain

    C. A. Rodríguez

  12. Hospital Ramón y Cajal, Madrid, Spain

    C. Crespo

  13. Centro Oncológico de Galicia, A Coruña, Spain

    M. Ramos

  14. Hospital de Cabueñes, Gijón, Spain

    J. M. Gracia-Marco

  15. Biomedical Research Institute INCLIVA, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain

    A. Lluch

  16. Hospital de Donostia, San Sebastián, Spain

    I. Álvarez

  17. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada

    E. Amir

  18. Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain

    M. Martin

  19. Complejo Hospitalario Universitario de Albacetee, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla la Mancha, Albacete, Spain

    A. Ocaña

  20. Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, 02006, Albacete, Spain

    A. Ocaña

Authors
  1. A. J. Templeton
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  2. Á. Rodríguez-Lescure
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  3. A. Ruíz
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  4. E. Alba
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  5. L. Calvo
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  6. M. Ruíz-Borrego
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  7. A. Santaballa
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  8. C. A. Rodríguez
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  9. C. Crespo
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  10. M. Ramos
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  11. J. M. Gracia-Marco
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  12. A. Lluch
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  13. I. Álvarez
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  14. M. I. Casas
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  15. M. Sánchez-Aragó
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  16. R. Caballero
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  17. E. Carrasco
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  18. E. Amir
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  19. M. Martin
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  20. A. Ocaña
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Consortia

the GEICAM 9906 Study Investigators

Corresponding author

Correspondence to A. Ocaña.

Ethics declarations

Ethical approval

The GEICAM 9906 study was approved by the ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Cite this article

Templeton, A.J., Rodríguez-Lescure, Á., Ruíz, A. et al. Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy. Clin Transl Oncol 20, 1548–1556 (2018). https://doi.org/10.1007/s12094-018-1885-5

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  • DOI: https://doi.org/10.1007/s12094-018-1885-5

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