Predictive Value of Inflammatory Indexes as Biomarkers of Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer Inflammatory indexes and NAC in BC
Abstract
Background: Breast cancer remains the most common cancer in women worldwide. Treatment has evolved into multimodal approaches, with pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) serving as a key prognostic marker. The aim of this study is to evaluate the value of inflammatory markers in predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer.
Methods: This cross sectional study of 74 breast cancer patients who underwent NAC followed by surgery included demographic, tumor, and immune-inflammatory marker data. ROC curve and Youden index determined optimal cutoffs. Univariate and multivariate logistic regression assessed associations between markers and pCR, adjusting for tumor stage, HER2, and ER status.
Results: Multivariate analysis identified pan immune inflammatory value (PIV), HER2, and ER status as significant independent predictors of pCR (p < 0.05). PIV (OR= 4.28, 95% CI 1.59-16.88, p=0.012) remained significant among inflammatory markers, while neutrophil to lymphocyte (NLR), monocyte to lymphocyte (MLR), and platelets to lymphocyte (PLR) did not. HER2-positive (OR=7.45, 95% CI 2.3-24.15, p=0.022) and hormone receotor (HR) negative (OR=7.02, 95% CI 2.63-18.7, p=0.02) statuses were also strongly associated with pCR.
Conclusion: PIV is a robust predictor of pCR in breast cancer patients receiving NAC, offering a comprehensive reflection of the immune-inflammatory state. Incorporating PIV with tumor-specific markers (e.g. Receptor status, Ki67, grade) may enhance treatment stratification. Further validation in diverse cohorts is warranted.
Full text article
References
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. 2021 May 4;71(3):209–49. doi: 10.3322/caac.21660
Cancer research [Internet]. [cited 2025 Jul 22]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer
Breast cancer in EU [Internet]. [cited 2025 Jul 22]. Available from: https://ecis.jrc.ec.europa.eu/pdf/Breast_cancer_2022-Oct_2023.pdf
Huang M, O’Shaughnessy J, Zhao J, Haiderali A, Cortés J, Ramsey SD, et al. Association of Pathologic Complete Response with Long-Term Survival Outcomes in Triple-Negative Breast Cancer: A Meta-Analysis. Cancer Res. 2020 Dec 15;80(24):5427–34. doi: 10.1158/0008-5472.CAN-20-1792
Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis. Clinical Cancer Research. 2020 Jun 15;26(12):2838–48. doi: 10.1158/1078-0432.CCR-19-3492
Mieog JSD, van der Hage JA, van de Velde CJH. Neoadjuvant chemotherapy for operable breast cancer. British Journal of Surgery. 2007 Sep 14;94(10):1189–200. doi: 10.1002/bjs.5894
Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis. JNCI Journal of the National Cancer Institute. 2005 Feb 2;97(3):188–94. doi: 10.1093/jnci/dji021
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy. Journal of Clinical Oncology. 2007 Oct 1;25(28):4414–22. doi: 10.1200/JCO.2007.10.6823
Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011 Mar;144(5):646–74. doi: 10.1016/j.cell.2011.02.013
Portale G, Bartolotta P, Azzolina D, Gregori D, Fiscon V. Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis. Langenbecks Arch Surg. 2023 Feb 13;408(1):85. doi: 10.1007/s00423-023-02786-8
Kumarasamy C, Tiwary V, Sunil K, Suresh D, Shetty S, Muthukaliannan GK, et al. Prognostic Utility of Platelet–Lymphocyte Ratio, Neutrophil–Lymphocyte Ratio and Monocyte–Lymphocyte Ratio in Head and Neck Cancers: A Detailed PRISMA Compliant Systematic Review and Meta-Analysis. Cancers (Basel). 2021 Aug 19;13(16):4166. doi: 10.3390/cancers13164166
Zhu H, Cao X. NLR members in inflammation-associated carcinogenesis. Cell Mol Immunol. 2017 May 3;14(5):403–5. doi: 10.1038/cmi.2017.14
Leon-Ferre RA, Whitaker KR, Suman VJ, Hoskin T, Giridhar K V., Moore RM, et al. Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer. Breast Cancer Research. 2024 Jun 10;26(1):97. doi: 10.1186/s13058-024-01848-z
Kim JY, Jung EJ, Kim JM, Lee HS, Kwag SJ, Park JH, et al. Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis. BMC Cancer. 2020 Dec 7;20(1):1206. doi: 10.1186/s12885-020-07700-9
Rönnau ADRO, Berto MD, Bica CG, Alves RV, Rotta LN. Platelet Concentration and Platelet/Lymphocyte Ratio as Prognostic Indicators in Luminal Breast Cancer. Journal of Molecular Pathology. 2023 Jan 2;4(1):15–27. doi: 10.3390/jmp4010002
Li F, Wang Y, Dou H, Chen X, Wang J, Xiao M. Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy. Front Oncol. 2024 Feb 6;14. doi: 10.3389/fonc.2024.1349021
Yildirim S, Dogan A, Akdag G, Yüksel Yasar Z, Bal H, Kinikoglu O, et al. The role of laboratory indices on treatment response and survival in breast cancer receiving neoadjuvant chemotherapy. Sci Rep. 2024 May 27;14(1):12123. doi: 10.1038/s41598-024-63096-7
Gasparri ML, Albasini S, Truffi M, Favilla K, Tagliaferri B, Piccotti F, et al. Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis. Ther Adv Med Oncol. 2023 Jan 15;15. doi: 10.1177/17588359231193732
Muñoz-Montaño W, Cabrera-Galeana P, Alvarado-Miranda A, Villarreal-Garza C, Mohar A, Olvera A, et al. Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer During Neoadjuvant Systemic Treatment. Clin Breast Cancer. 2020 Aug;20(4):307-316.e1. doi: 10.1016/j.clbc.2019.12.011
Truffi M, Sottotetti F, Gafni N, Albasini S, Piccotti F, Morasso C, et al. Prognostic Potential of Immune Inflammatory Biomarkers in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. Cancers (Basel). 2022 Oct 27;14(21):5287. doi: 10.3390/cancers14215287
Dan J, Tan J, Huang J, Yuan Z, Guo Y. Early changes of platelet lymphocyte ratio correlate with neoadjuvant chemotherapy response and predict pathological complete response in breast cancer. Mol Clin Oncol. 2023 Sep 25;19(5):90. doi: 10.3892/mco.2023.2686
Tiainen S, Rilla K, Hämäläinen K, Oikari S, Auvinen P. The prognostic and predictive role of the neutrophil-to-lymphocyte ratio and the monocyte-to-lymphocyte ratio in early breast cancer, especially in the HER2+ subtype. Breast Cancer Res Treat. 2021 Jan 18;185(1):63–72. doi: 10.1007/s10549-020-05925-7
Bae SJ, Cha YJ, Yoon C, Kim D, Lee J, Park S, et al. Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy. Sci Rep. 2020 Aug 4;10(1):13078. doi: 10.1038/s41598-020-69965-1
Buyuksimsek M, Ogul A, Mirilli C, Paydas S. Inflammatory Markers Predicting Pathological Complete Response in Cases with Breast Cancer Treated by Neoadjuvant Chemotherapy. Eur J Breast Health. 2020 Sep 24;16(4):229–34. doi: 10.5152/ejbh.2020.5556
Li F, Wang Y, Dou H, Chen X, Wang J, Xiao M. Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy. Front Oncol. 2024 Feb 6;14. doi: 10.3389/fonc.2024.1349021
Yang ZJ, Xin F, Chen ZJ, Yu Y, Wang X, Cao XC. Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer. BMC Cancer. 2024 Jan 25;24(1):134. doi: 10.1186/s12885-024-11871-0
Authors
Copyright (c) 2025 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.