Liu Qiuge, Fang Shuangshuang, Liang Shanshan, Lv Jinyan, Wang Gang, Tang Rongbin, Ji Xuening, Zhao Tong, Li Jiaoyang, Xu Lu, Ma Lianli, Wang Ruoyu, Li Heming
Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian, China.
Transl Cancer Res. 2020 Nov;9(11):7065-7078. doi: 10.21037/tcr-20-2157.
The activation of inflammation and coagulation cascades plays an essential role in the development of various malignancies, including metastatic breast cancer (MBC). This retrospective study aimed to investigate the prognostic role of the combination of fibrinogen and the inflammation-based index in patients with MBC.
A total of 176 patients with MBC were retrospectively reviewed. The clinical and pathological data of included patients were followed-up and analyzed. The plasma fibrinogen concentration (FIB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. Dynamic variations in the FIB, NLR, and PLR values were collected from 56 MBC patients before and after first-line therapy. Receiver operating characteristic (ROC) curves were constructed to assess the optimal cut-off values. Correlations between FIB and NLR or PLR were evaluated using Spearman correlation analysis. The Kaplan-Meier method, two-tailed log-rank test, and Cox proportional hazard model were used for statistical analysis.
Baseline FIB was positively correlated with NLR and PLR values in MBC patients (P<0.05). Additionally, multivariable analysis proved that the ERBB2 + subtype (P=0.023), basal-like subtype (P=0.032), targeted therapy (P=0.033), other regimens (P=0.005), and baseline FIB level (P=0.004) were independent prognostic variables for progression-free survival (PFS) in MBC patients. Furthermore, ERBB2+, basal-like subtypes, and baseline hyperfibrinogenemia were independent factors for poor prognosis in MBC patients [hazard ratio (HR): 3.717, 95% confidence interval (CI): 1.561-8.851, P=0.003; HR: 3.245, 95% CI: 1.368-7.698, P=0.008; HR: 2.069, 95% CI: 1.352-3.167, P=0.001, respectively]. Most importantly, the FIB level increased significantly after first-line therapy in patients with disease progression (3.73±0.63 5.32±0.52 g/L, P=0.042) and also decreased markedly in stable disease (3.42±1.05 3.03±0.73 g/L, P=0.036). However, PFS and overall survival (OS) were not significantly correlated with the dynamic changes of FIB and the inflammation-based index.
The present study provided evidence that baseline FIB combined with NLR and PLR could serve as prognostic predictors for MBC patients. Dynamic change of FIB before and after first-line therapy could also be used as a potential predictor of therapeutic response in MBC patients.
炎症和凝血级联反应的激活在包括转移性乳腺癌(MBC)在内的各种恶性肿瘤的发展中起着至关重要的作用。本回顾性研究旨在探讨纤维蛋白原与基于炎症的指标联合应用对MBC患者的预后价值。
回顾性分析176例MBC患者的临床资料。收集并分析纳入患者的临床和病理数据。检测血浆纤维蛋白原浓度(FIB)、中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)。收集56例MBC患者一线治疗前后FIB、NLR和PLR值的动态变化。绘制受试者工作特征(ROC)曲线以评估最佳临界值。采用Spearman相关分析评估FIB与NLR或PLR之间的相关性。采用Kaplan-Meier法、双侧对数秩检验和Cox比例风险模型进行统计分析。
MBC患者基线FIB与NLR和PLR值呈正相关(P<0.05)。此外,多变量分析证明,ERBB2 +亚型(P = 0.023)、基底样亚型(P = 0.032)、靶向治疗(P = 0.033)、其他方案(P = 0.005)和基线FIB水平(P = 0.004)是MBC患者无进展生存期(PFS)的独立预后变量。此外,ERBB2 +、基底样亚型和基线高纤维蛋白原血症是MBC患者预后不良的独立因素[风险比(HR):3.717,95%置信区间(CI):1.561 - 8.851,P = 0.003;HR:3.245,95% CI:1.368 - 7.698,P = 0.008;HR:2.069,95% CI:1.352 - 3.167,P = 0.001]。最重要的是,疾病进展患者一线治疗后FIB水平显著升高(3.73±0.63 5.32±0.52 g/L,P = 0.042),病情稳定患者FIB水平也显著降低(3.42±1.05 3.03±0.73 g/L,P = 0.036)。然而,PFS和总生存期(OS)与FIB和基于炎症的指标的动态变化无显著相关性。
本研究表明,基线FIB联合NLR和PLR可作为MBC患者的预后预测指标。一线治疗前后FIB的动态变化也可作为MBC患者治疗反应的潜在预测指标。