Single Center Study: Using Pre-Treatment Neutrophil to Lymphocyte Ratio as a Predictor of Outcome in Metastatic Breast Cancer Patients Treated with Cyclin Dependent Kinase 4/6 Inhibitors
DOI:
https://doi.org/10.70749/ijbr.v3i7.1877Keywords:
Hematologic biomarkers, prognostic indicators, lymphopenia, survival analysis, low- and middle-income countries (LMICs)Abstract
Introduction: Breast cancer is the most prevalent cancer among women worldwide, and prognostic markers are vital for predicting outcomes. Systemic inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and lymphopenia, have been associated with tumor progression and prognosis. This study aimed to assess the predictive effects of NLR, LMR, and lymphopenia in Pakistani women receiving CDK4/6 inhibitors alongside endocrine therapy for metastatic breast cancer. Materials and Methods: We conducted a retrospective study at Aga Khan University Hospital, Karachi, from January 2018 to September 2024. Blood tests conducted within one week before treatment initiation were analyzed for NLR, LMR, and lymphopenia. Results: Among 53 evaluable patients, those with pre-treatment NLR <2.5 had a median progression-free survival (PFS) of 14 months versus 8 months for NLR ≥2.5. Median overall survival (OS) was 24 months (95% CI: 18.4–29.0) for NLR <2.5 and 20 months (95% CI: 14.7–25.2) for NLR ≥2.5. Patients with LMR >3.3 had a median OS of 14 months (95% CI: 9.71–18.29) compared to 12 months (95% CI: 8.4–15.96) for LMR ≤3.3. Lymphopenia patients had a median PFS of 8.0 months (95% CI: 1.78–14.22), while those with normal lymphocyte counts had a PFS of 14.0 months (95% CI: 11.20–16.81). Conclusion: NLR, LMR, and lymphopenia are accessible, cost-effective biomarkers that may aid in prognostication and treatment planning for metastatic breast cancer patients receiving CDK4/6 inhibitors.
Downloads
References
1. Bray Bsc F, Laversanne | Mathieu, Hyuna |, Phd S, Ferlay J, Siegel Mph RL, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin [Internet]. 2024 May 1 [cited 2025 Feb 4];74(3):229–63.
https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21834
2. Rehman MA, Tahir E, Hussain HG, Khalid A, Taqi SM, Meenai EA. Awareness regarding breast cancer amongst women in Pakistan: A systematic review and meta-analysis. PLoS One [Internet]. 2024 Mar 1 [cited 2025 Feb 4];19(3):e0298275.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10919669
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin [Internet]. 2021 May [cited 2025 Feb 4];71(3):209–49.
https://pubmed.ncbi.nlm.nih.gov/33538338
4. O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist [Internet]. 2005 Oct 1 [cited 2025 Feb 4];10 Suppl 3(S3):20–9.
https://pubmed.ncbi.nlm.nih.gov/16368868
5. Burstein HJ. Systemic Therapy for Estrogen Receptor–Positive, HER2-Negative Breast Cancer. New England Journal of Medicine [Internet]. 2020 Dec 24 [cited 2025 Feb 4];383(26):2557–70.
https://www.nejm.org/doi/abs/10.1056/NEJMra1307118
6. Lindeman GJ, Fernando TM, Bowen R, Jerzak KJ, Song X, Decker T, et al. VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors – Efficacy, Safety, and Biomarker Results. Clinical Cancer Research [Internet]. 2022 Aug 1 [cited 2025 Feb 4];28(15):3256.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9662928
7. Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med [Internet]. 2018 Nov 15 [cited 2025 Feb 4];379(20):1926–36.
https://pubmed.ncbi.nlm.nih.gov/30345905
8. Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2: A Randomized Clinical Trial. JAMA Oncol [Internet]. 2019 Jan 1 [cited 2025 Feb 4];6(1):116.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6777264
9. Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer [Internet]. 2019 Dec 1 [cited 2025 Feb 4];5(1):5.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6336880
10. Rottier P, Emile G, Johnson A, Levy C, Allouache D, Hrab I, et al. Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors. Front Oncol [Internet]. 2023 Jan 19 [cited 2025 Apr 17];12.
https://pubmed.ncbi.nlm.nih.gov/36741710
11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell [Internet]. 2011 Mar 4 [cited 2025 Apr 16];144(5):646–74.
https://pubmed.ncbi.nlm.nih.gov/21376230
12. Pagès F, Galon J, Dieu-Nosjean MC, Tartour E, Sautès-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene [Internet]. 2010 Feb [cited 2025 Apr 16];29(8):1093–102.
https://pubmed.ncbi.nlm.nih.gov/19946335
13. Coussens LM, Werb Z. Inflammation and cancer. Nature [Internet]. 2002 Dec 26 [cited 2025 Apr 16];420(6917):860–7.
https://pubmed.ncbi.nlm.nih.gov/12490959
14. Guthrie GJK, Charles KA, Roxburgh CSD, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol [Internet]. 2013 Oct [cited 2025 Apr 16];88(1):218–30.
https://pubmed.ncbi.nlm.nih.gov/23602134
15. Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O’reilly DSJ, et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer [Internet]. 2011 Nov [cited 2025 Apr 16];47(17):2633–41.
https://pubmed.ncbi.nlm.nih.gov/21724383
16. Dirican A, Kucukzeybek BB, Alacacioglu A, Kucukzeybek Y, Erten C, Varol U, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer? Int J Clin Oncol [Internet]. 2015 Feb 1 [cited 2025 Apr 16];20(1):70–81.
https://pubmed.ncbi.nlm.nih.gov/24532163
17. Noh H, Eomm M, Han A. Usefulness of pretreatment neutrophil to lymphocyte ratio in predicting disease-specific survival in breast cancer patients. J Breast Cancer [Internet]. 2013 Mar [cited 2025 Apr 16];16(1):55–9.
https://pubmed.ncbi.nlm.nih.gov/23593082
18. Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer [Internet]. 2015 Jun 30 [cited 2025 Apr 16];113(1):150–8.
https://pubmed.ncbi.nlm.nih.gov/26022929
19. Ma Y, Zhang J, Chen X. Lymphocyte-to-Monocyte Ratio is Associated with the Poor Prognosis of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancer Manag Res [Internet]. 2021 [cited 2025 Apr 16];13:1571–80.
https://pubmed.ncbi.nlm.nih.gov/33623436
20. Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res [Internet]. 2017 Jan 5 [cited 2025 Apr 20];19(1).
https://pubmed.ncbi.nlm.nih.gov/28057046
21. Liu X, Qu JK, Zhang J, Yan Y, Zhao XX, Wang JZ, et al. Prognostic role of pretreatment neutrophil to lymphocyte ratio in breast cancer patients: A meta-analysis. Medicine [Internet]. 2017 Nov 1 [cited 2025 Apr 20];96(45). https://pubmed.ncbi.nlm.nih.gov/29137007
22. Wei B, Yao M, Xing C, Wang W, Yao J, Hong Y, et al. The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis. Onco Targets Ther [Internet]. 2016 Sep 8 [cited 2025 Apr 20];9:5567–75.
https://pubmed.ncbi.nlm.nih.gov/27660475
23. Manuel M, Trédan O, Bachelot T, Clapisson G, Courtier A, Parmentier G, et al. Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients. Oncoimmunology [Internet]. 2012 [cited 2025 Apr 19];1(4):432.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3382902
24. Borg C, Ray-Coquard I, Philip I, Clapisson G, Bendriss-Vermare N, Menetrier-Caux C, et al. CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer. Cancer [Internet]. 2004 Dec 1 [cited 2025 Apr 19];101(11):2675–80.
https://pubmed.ncbi.nlm.nih.gov/15503313
25. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res [Internet]. 2009 Jul 1 [cited 2025 Apr 19];69(13):5383–91.
https://pubmed.ncbi.nlm.nih.gov/19549917
26. Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol [Internet]. 2011 May 20 [cited 2025 Apr 20];29(15):1949–55.
https://pubmed.ncbi.nlm.nih.gov/21483002
27. Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature [Internet]. 2015 Jun 18 [cited 2025 Apr 20];522(7556):345–8.
https://pubmed.ncbi.nlm.nih.gov/25822788
28. Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, et al. CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov [Internet]. 2018 Feb 1 [cited 2025 Apr 20];8(2):216–33.
https://pubmed.ncbi.nlm.nih.gov/29101163
29. Goel S, Decristo MJ, Watt AC, Brinjones H, Sceneay J, Li BB, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature [Internet]. 2017 Aug 24 [cited 2025 Apr 20];548(7668):471–5.
https://pubmed.ncbi.nlm.nih.gov/28813415
30. Wariss BR, de Souza Abrahão K, de Aguiar SS, Bergmann A, Thuler LCS. Effectiveness of four inflammatory markers in predicting prognosis in 2374 women with breast cancer. Maturitas [Internet]. 2017 Jul 1 [cited 2025 Apr 20];101:51–6.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research

This work is licensed under a Creative Commons Attribution 4.0 International License.