Skip to main content

Advertisement

SpringerLink
Log in

The dynamic change of neutrophil to lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure1

Similar content being viewed by others

References:s

  1. 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.

    Article  Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. Untch M, Konecny GE, Paepke S, von Minckwitz G. Current and future role of neoadjuvant therapy for breast cancer. Breast. 2014;23:526–37.

    Article  Google Scholar 

  4. Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, et al. Primary systemic therapy of breast cancer. Oncologist. 2006;11:574–89.

    Article  CAS  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA. 2011;306:2608–9.

    Article  CAS  Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. Cortazar P, Geyer CJ. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol. 2015;22:1441–6.

    Article  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  CAS  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. 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.

    CAS  Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. 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.

    Article  Google Scholar 

  30. 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.

    Article  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. 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.

    Article  Google Scholar 

  33. 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.

    PubMed  PubMed Central  Google Scholar 

  34. 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.

    Article  Google Scholar 

  35. 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.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Scientific Research Project of Sichuan provincial Health and Family Planning Commission (No. 16PJ058)

Author information

Author notes

  1. Jiaqiang Dan and Jinya Tan contributed to this work equally.

Authors and Affiliations

  1. Department of Breast Surgery, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China

    Jiaqiang Dan, Junhua Huang, Xiaoli Zhang, Yao Guo, Yunkun Huang & Jin Yang

  2. Department of Rheumatology and Immunology, Wenjiang District People’s Hospital of Chengdu City, Chengdu, 611130, Sichuan, People’s Republic of China

    Jinya Tan

Authors
  1. Jiaqiang Dan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jinya Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junhua Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoli Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunkun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiaqiang Dan.

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

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-020-01096-x

Keywords

Search

Navigation