Abstract
Background
The pre-treatment neutrophil–lymphocyte ratio (NLR) has been reported to be a predictive factor for pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer patients. However, whether the dynamic change of post-treatment neutrophil to lymphocyte ratio (delta-NLR) can better predict the same outcome remains unclear.
Materials and methods
We retrospectively analyzed 242 consecutive patients affected by breast cancer and candidates of NACT. The complete blood cell counts before and after NACT were evaluated to calculate NLR. The relationships between delta-NLR and pCR, along with other clinical-pathological characteristics were analyzed. Univariate and multivariate analyses were performed using a logistic regression model.
Results
Of the 242 patients, 65 (26.9%) achieved a pCR. Pre-treatment NLR and post-treatment NLR were not significantly associated with pCR if analyzed separately in multivariate analyses. However, when combining together, patients with delta-NLR < 0 profile achieved a significantly higher rate of pCR compared to those with delta-NLR ≥ 0 (OR 2.84, 95% CI 1.35–5.96, p = 0.006). Additionally, the predictive value of delta-NLR was independent from common prognostic factors such as Ki-67, and molecular subtypes.
Conclusions
Delta-NLR, rather than pre-treatment or post-treatment NLR is associated with pCR rate, suggesting that the dynamic change of NLR may be an important factor predicting the response to NACT in breast cancer patients.
Similar content being viewed by others
References:s
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.
Untch M, Konecny GE, Paepke S, von Minckwitz G. Current and future role of neoadjuvant therapy for breast cancer. Breast. 2014;23:526–37.
Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, et al. Primary systemic therapy of breast cancer. Oncologist. 2006;11:574–89.
Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;2001:96–102.
Bossuyt V, Provenzano E, Symmans WF, Boughey JC, Coles C, et al. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015;26:1280–91.
Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA. 2011;306:2608–9.
Wang-Lopez Q, Chalabi N, Abrial C, Radosevic-Robin N, Durando X, et al. Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer? Crit Rev Oncol Hematol. 2015;95:88–104.
Li X, Dai D, Chen B, Tang H, Wei W. Oncological outcome of complete response after neoadjuvant chemotherapy for breast conserving surgery: a systematic review and meta-analysis. World J Surg Oncol. 2017;15:210.
Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Symmans WF, et al. Tumor biology and response to chemotherapy impact breast cancer-specific survival in node-positive breast cancer patients treated with neoadjuvant chemotherapy: long-term follow-up from ACOSOG Z1071 (alliance). Ann Surg. 2017;266:667–76.
Cortazar P, Geyer CJ. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol. 2015;22:1441–6.
Diaz-Botero S, Espinosa-Bravo M, Goncalves VR, Esgueva-Colmenarejo A, Peg V, et al. Different prognostic implications of residual disease after neoadjuvant treatment: impact of Ki 67 and site of response. Ann Surg Oncol. 2016;23:3831–7.
Koh YW, Lee HJ, Ahn JH, Lee JW, Gong G. Prognostic significance of the ratio of absolute neutrophil to lymphocyte counts for breast cancer patients with ER/PR-positivity and HER2-negativity in neoadjuvant setting. Tumour Biol. 2014;35:9823–30.
Asano Y, Kashiwagi S, Onoda N, Noda S, Kawajiri H, et al. Predictive value of neutrophil/lymphocyte ratio for efficacy of preoperative chemotherapy in triple-negative breast cancer. Ann Surg Oncol. 2016;23:1104–10.
Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486.
Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30:1073–81.
Graziano V, Grassadonia A, Iezzi L, Vici P, Pizzuti L, et al. Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast. 2019;44:33–8.
Chen Y, Chen K, Xiao X, Nie Y, Qu S, et al. Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. BMC Cancer. 2016;16:320.
Chae S, Kang KM, Kim HJ, Kang E, Park SY, et al. Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer. Curr Oncol. 2018;25:e113–e11919.
Pennisi A, Kieber-Emmons T, Makhoul I, Hutchins L. Relevance of pathological complete response after neoadjuvant therapy for breast cancer. Breast Cancer (Auckl). 2016;10:103–6.
Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol. 2013;31:3997–4013.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, et al. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.
Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6:283–7.
Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer. 2004;90:206–15.
De Larco JE, Wuertz BR, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res. 2004;10:4895–900.
Queen MM, Ryan RE, Holzer RG, Keller-Peck CR, Jorcyk CL. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 2005;65:8896–904.
Ding PR, An X, Zhang RX, Fang YJ, Li LR, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer. Int J Colorectal Dis. 2010;25:1427–33.
Lee HJ, Seo JY, Ahn JH, Ahn SH, Gong G. Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer. 2013;16:32–9.
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19:40–50.
Paramanathan A, Saxena A, Morris DL. A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol. 2014;23:31–9.
Wang F, Liu ZY, Xia YY, Zhou C, Shen XM, et al. Changes in neutrophil/lymphocyte and platelet/lymphocyte ratios after chemotherapy correlate with chemotherapy response and prediction of prognosis in patients with unresectable gastric cancer. Oncol Lett. 2015;10:3411–8.
Mori M, Shuto K, Kosugi C, Narushima K, Hayashi H, et al. An increase in the neutrophil-to-lymphocyte ratio during adjuvant chemotherapy indicates a poor prognosis in patients with stage II or III gastric cancer. BMC Cancer. 2018;18:1261.
Hyder J, Boggs DH, Hanna A, Suntharalingam M, Chuong MD. Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during chemoradiation predict for survival and pathologic complete response in trimodality esophageal cancer patients. J Gastrointest Oncol. 2016;7:189–95.
Dan JQ, Zhang YJ, Huang JT, Chen MS, Gao HJ, et al. Hepatitis B virus reactivation after radiofrequency ablation or hepatic resection for HBV-related small hepatocellular carcinoma: a retrospective study. Eur J Surg Oncol. 2013;39:865–72.
Li Z, Zhao R, Cui Y, Zhou Y, Wu X. The dynamic change of neutrophil to lymphocyte ratio can predict clinical outcome in stage I–III colon cancer. Sci Rep. 2018;8:9453.
Acknowledgements
This work was supported by the Scientific Research Project of Sichuan provincial Health and Family Planning Commission (No. 16PJ058)
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
The work has been approved by the local ethical committee.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Dan, J., Tan, J., Huang, J. et al. The dynamic change of neutrophil to lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer 27, 982–988 (2020). https://doi.org/10.1007/s12282-020-01096-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12282-020-01096-x