Low plasma IL-8 levels during chemotherapy are predictive of excellent long-term survival in metastatic breast cancer

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p><em>Background:</em> 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.</p><p><em>Patients and Methods:</em> 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.</p><p><em>Results:</em> 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; <em>P</em> = .012) and 3 (n = 6; age-adjusted HR = 8.65; 95% confidence interval, 3.16–23.7; <em>P</em> < .001).</p><p><em>Conclusion:</em> Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.</p></div>