Correlation between peripheral blood inflammatory indicators and pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer patients

Tulay Eren, Cengiz Karacin, Gokhan Ucar, Yakup Ergun, Ozan Yazici, Goksen İnanc İmamoglu, Nuriye Ozdemir, Tulay Eren, Cengiz Karacin, Gokhan Ucar, Yakup Ergun, Ozan Yazici, Goksen İnanc İmamoglu, Nuriye Ozdemir

Abstract

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (-ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 μL, 2000 μL, 635 μL, 271 × 10 μL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.

References

    1. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 2005;97:188–94.
    1. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008;26:1275–81.
    1. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164–72.
    1. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30:1796–804.
    1. Zhang F, Huang M, Zhou H, et al. A nomogram to predict the pathologic complete response of neoadjuvant chemotherapy in triple-negative breast cancer based on simple laboratory indicators. Ann Surg Oncol 2019;26:3912–9.
    1. Mou P, Wang H, An L, et al. RS7435335 located in the UGT2B7 gene may be a possible genetic marker for the clinical response and prognosis of breast cancer patients receiving neoadjuvant chemotherapy. J Cell Biochem 2018;doi: 10.1002/jcb.27990.
    1. Du Y, Zhou L, Lin Y, et al. Polymorphisms in microRNA let-7 binding sites of the HIF1AN and CLDN12 genes can predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in breast cancer. Ann Transl Med 2019;7:138.
    1. Luo G, Guo M, Liu Z, et al. Blood neutrophil–lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy. Ann Surg Oncol 2015;22:670–6.
    1. Ku JH, Kang M, Kim H, et al. The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy. Br J Cancer 2015;112:461.
    1. Seah J-A, Leibowitz-Amit R, Atenafu EG, et al. Neutrophil-lymphocyte ratio and pathological response to neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. Clin Genitourinary Cancer 2015;13:e229–33.
    1. Schmidt H, Suciu S, Punt CJ, et al. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol 2007;25:1562.
    1. Azab B, Shah N, Radbel J, et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol 2013;30:432.
    1. 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 2013;16:55–9.
    1. Koh C, Bhoo-Pathy N, Ng K, et al. Utility of pre-treatment neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer 2015;113:150.
    1. Hu RJ, Liu Q, Ma JY, et al. Preoperative lymphocyte-to-monocyte ratio predicts breast cancer outcome: a meta-analysis. Clin Chim Acta 2018;484:1–6.
    1. Rivas M, Acevedo F, Dominguez F, et al. The neutrophil to lymphocyte ratio predicts the response to neoadjuvant chemotherapy in luminal B breast cancer. Asian Pac J Cancer Prev 2019;20:2209–12.
    1. Asano Y, Kashiwagi S, Onoda N, 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.
    1. Suppan C, Bjelic-Radisic V, La Garde M, et al. Neutrophil/lymphocyte ratio has no predictive or prognostic value in breast cancer patients undergoing preoperative systemic therapy. BMC Cancer 2015;15:1027.
    1. Eryilmaz MK, Mutlu H, Salim DK, et al. The neutrophil to lymphocyte ratio has a high negative predictive value for pathologic complete response in locally advanced breast cancer patients receiving neoadjuvant chemotherapy. Asian Pac J Cancer Prev 2014;15:7737–40.
    1. Asano Y, Kashiwagi S, Onoda N, et al. Platelet–lymphocyte ratio as a useful predictor of the therapeutic effect of neoadjuvant chemotherapy in breast cancer. PLoS One 2016;11:e0153459.
    1. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–4.
    1. Kim HY, Kim TH, Yoon HK, et al. The role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in predicting neoadjuvant chemotherapy response in breast cancer. J Breast Cancer 2019;22:425–38.
    1. Battisti NML, True V, Chaabouni N, et al. Pathological complete response to neoadjuvant systemic therapy in 789 early and locally advanced breast cancer patients: the Royal Marsden experience. Breast Cancer Res Treat 2019;doi: 10.1007/s10549-019-05444-0. Epub 2019 Sep 18.
    1. Guarneri V, Broglio K, Kau S-W, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 2006;24:1037–44.
    1. Jarzab M, Stobiecka E, Badora-Rybicka A, et al. Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively. Pol J Pathol 2019;70:91–9.
    1. Vila J, Mittendorf EA, Farante G, et al. Nomograms for predicting axillary response to neoadjuvant chemotherapy in clinically node-positive patients with breast cancer. Ann Surg Oncol 2016;23:3501–9.
    1. Choi HJ, Ryu JM, Kim I, et al. Nomogram for accurate prediction of breast and axillary pathologic response after neoadjuvant chemotherapy in node positive patients with breast cancer. Ann Surg Treat Res 2019;96:169–76.

Source: PubMed

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