A J Templeton1,2, Á Rodríguez-Lescure3,4, A Ruíz4,5, E Alba4,6,7, L Calvo4,8, M Ruíz-Borrego4,9, A Santaballa4,10, C A Rodríguez4,11, C Crespo4,12, M Ramos4,13, J M Gracia-Marco4,14, A Lluch4,7,15, I Álvarez4,16, M I Casas4, M Sánchez-Aragó4, R Caballero4, E Carrasco4, E Amir17, M Martin4,7,18, A Ocaña19,20,21. 1. Department of Medical Oncology, St. Claraspital, Basel, Switzerland. 2. Faculty of Medicine, University of Basel, Basel, Switzerland. 3. Hospital Universitario de Elche, Elche, Spain. 4. GEICAM (Spanish Breast Cancer Group), Madrid, Spain. 5. Instituto Valenciano de Oncología, Valencia, Spain. 6. Hospital Virgen de la Victoria, Málaga, Spain. 7. Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain. 8. Complejo Hospitalario Juan Canalejo, A Coruña, Spain. 9. Hospital Univ. Virgen del Rocío, Seville, Spain. 10. Hospital Universitario La Fe, Valencia, Spain. 11. Hospital Clínico Universitario de Salamanca, Salamanca (IBSAL), Salamanca, Spain. 12. Hospital Ramón y Cajal, Madrid, Spain. 13. Centro Oncológico de Galicia, A Coruña, Spain. 14. Hospital de Cabueñes, Gijón, Spain. 15. Biomedical Research Institute INCLIVA, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain. 16. Hospital de Donostia, San Sebastián, Spain. 17. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. 18. Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. 19. GEICAM (Spanish Breast Cancer Group), Madrid, Spain. albertoo@sescam.jccm.es. 20. Complejo Hospitalario Universitario de Albacetee, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla la Mancha, Albacete, Spain. albertoo@sescam.jccm.es. 21. Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, 02006, Albacete, Spain. albertoo@sescam.jccm.es.
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).
RCT Entities:
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).
Entities:
Keywords:
Breast cancer; Neutrophil–lymphocyte ratio; PAM50; Prognosis; Survival
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