Gao Siming, Tang Wenjie, Zuo Bingli, Mulvihill Lianne, Yu Jinming, Yu Yishan
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Front Oncol. 2023 Jan 16;12:1065606. doi: 10.3389/fonc.2022.1065606. eCollection 2022.
Previous studies have reported that neutrophil-to-lymphocyte ratio (NLR) at pre-treatment was predictive for overall survival (OS) and pathologic complete response (pCR) in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC). This study aims to explore the predictive role of both pre- and post-NLR for OS as well as longitudinal NLR kinetics towards pCR in BC patients undergoing NAC.
We retrospectively included 501 BC patients who received NAC from 2009 to 2018. NLR at pre-, mid (every two cycles of NAC)-, and post-treatment were collected. Overall, 421 patients were included in the survival analysis. These patients were randomly divided into a training cohort ( = 224) and a validation cohort ( = 197). A multivariable Cox model was built using all significant factors in the multivariable analysis from the training cohort. The performance of the model was verified in the validation cohort by the concordance index (C-index). Longitudinal analysis for pCR prediction of NLR was performed using a mixed-effects regression model among 176 patients who finished eight cycles of NAC.
The median follow-up time was 43.2 months for 421 patients. In the training cohort, multivariable analysis revealed that ER status, clinical node stage, pCR, pre-NLR, and post-NLR (all < 0.05) were independent predictors of OS. The OS nomogram was established based on these parameters. The C-indexes of the nomogram were 0.764 and 0.605 in the training and validation cohorts, respectively. In the longitudinal analysis, patients who failed to achieve pCR experienced an augment of NLR during NAC while NLR remained stable among patients with pCR. Pre-NLR tended to be significantly associated with OS in patients of HER2 overexpressing and TNBC subtypes (all < 0.05), but not in Luminal A and Luminal B subtypes.
This study demonstrated the prognostic value of both pre-NLR and post-NLR on clinical outcomes in BC patients receiving NAC. A novel nomogram was established to predict OS. Non-pCR patients developed increased NLRs during NAC. Routine assessment of NLR may be a simple and affordable tool to predict prognosis for BC patients receiving NAC.
既往研究报道,接受新辅助化疗(NAC)的乳腺癌(BC)患者治疗前的中性粒细胞与淋巴细胞比值(NLR)可预测总生存期(OS)和病理完全缓解(pCR)。本研究旨在探讨治疗前和治疗后的NLR对接受NAC的BC患者OS的预测作用,以及NLR纵向动力学对pCR的影响。
我们回顾性纳入了2009年至2018年期间接受NAC的501例BC患者。收集治疗前、治疗中期(每两个周期NAC)和治疗后的NLR。总体而言,421例患者纳入生存分析。这些患者被随机分为训练队列(n = 224)和验证队列(n = 197)。使用训练队列多变量分析中的所有显著因素构建多变量Cox模型。通过一致性指数(C-index)在验证队列中验证模型的性能。对完成8个周期NAC的176例患者,使用混合效应回归模型对NLR预测pCR进行纵向分析。
421例患者的中位随访时间为43.2个月。在训练队列中,多变量分析显示,雌激素受体(ER)状态、临床淋巴结分期、pCR、治疗前NLR和治疗后NLR(均P < 0.05)是OS的独立预测因素。基于这些参数建立了OS列线图。该列线图在训练队列和验证队列中的C-index分别为0.764和0.605。在纵向分析中,未达到pCR的患者在NAC期间NLR升高,而pCR患者的NLR保持稳定。治疗前NLR在人表皮生长因子受体2(HER2)过表达和三阴乳腺癌(TNBC)亚型患者中往往与OS显著相关(均P < 0.05),但在腔面A型和腔面B型亚型中并非如此。
本研究证明了治疗前和治疗后的NLR对接受NAC的BC患者临床结局的预后价值。建立了一种新的列线图来预测OS。未达到pCR的患者在NAC期间NLR升高。常规评估NLR可能是预测接受NAC的BC患者预后的一种简单且经济的工具。