Department of Oncology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland.
The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
Clin Breast Cancer. 2019 Aug;19(4):e522-e533. doi: 10.1016/j.clbc.2019.03.006. Epub 2019 Apr 4.
Interleukin (IL)-8 is a proinflammatory cytokine, and high levels of IL-8 are associated with poor prognosis in many malignancies. The objective of this study was to explore the clinical benefit of monitoring plasma IL-8 levels during breast cancer chemotherapy.
We conducted an exploratory analysis of several circulating proteins, including IL-8, in the plasma. Plasma samples were obtained from 58 metastatic breast cancer patients who took part in a prospective phase 2 first-line bevacizumab chemotherapy trial. Samples were analyzed before therapy, after 6 weeks and 6 months of treatment, and at the final study visit. On the basis of a trajectory analysis of the plasma IL-8 levels, the patients were divided into 3 trajectory groups.
Plasma IL-8, IL-6, IL-18, matrix metalloproteinase (MMP)-2, MMP-9, YKL-40, resistin, and high-mobility group box 1 (HMGB1) concentrations were measured, and the most pronounced predictor of patient survival was IL-8. On the basis of the trajectory analysis of the IL-8 levels, the majority of patients (n = 35, 60%) belonged to trajectory group 1, and these patients had significantly lower IL-8 levels before and during the entire chemotherapy treatment period than did the patients in the other groups. Trajectory group 1 patients had significantly better overall survival compared to patients in trajectory group 2 (n = 17; age-adjusted HR = 2.45; 95% confidence interval, 1.21-5.97; P = .012) and 3 (n = 6; age-adjusted HR = 8.65; 95% confidence interval, 3.16-23.7; P < .001).
Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.
白细胞介素（IL）-8 是一种促炎细胞因子，许多恶性肿瘤中高水平的 IL-8 与预后不良相关。本研究旨在探讨监测乳腺癌化疗过程中血浆 IL-8 水平的临床获益。
我们对包括 IL-8 在内的几种循环蛋白进行了探索性分析。58 名转移性乳腺癌患者参加了一项前瞻性的一线贝伐珠单抗化疗试验，采集了他们的血浆样本。在治疗前、治疗 6 周和 6 个月以及最后一次研究访视时分析了这些样本。基于血浆 IL-8 水平的轨迹分析，将患者分为 3 个轨迹组。
测量了血浆 IL-8、IL-6、IL-18、基质金属蛋白酶（MMP）-2、MMP-9、YKL-40、抵抗素和高迁移率族蛋白 B1（HMGB1）浓度，对患者生存最具预测性的因素是 IL-8。基于 IL-8 水平的轨迹分析，大多数患者（n=35，60%）属于轨迹组 1，这些患者在整个化疗治疗期间的 IL-8 水平明显低于其他组。与轨迹组 2（n=17；年龄调整的 HR=2.45；95%置信区间，1.21-5.97；P=0.012）和 3（n=6；年龄调整的 HR=8.65；95%置信区间，3.16-23.7；P<0.001）相比，轨迹组 1 患者的总生存期明显更好。
化疗期间的低 IL-8 水平可能有助于识别生存时间延长的患者。
