Low Plasma IL-8 Levels During Chemotherapy Are Predictive of Excellent Long-Term Survival in Metastatic Breast Cancer.

Abstract

BACKGROUND:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.

• Authors: Leena Tiainen, Mari Hämäläinen, Tiina Luukkaala, Minna Tanner, Outi Lahdenperä, Pia Vihinen, Arja Jukkola, Peeter Karihtala, Eeva Moilanen, Pirkko-Liisa Kellokumpu-Lehtinen
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 19 Issue 4 Pg. e522-e533 (08 2019) ISSN: 1938-0666 [Electronic] United States
• PMID: 31029558 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• CXCL8 protein, human
• Interleukin-8
• Receptors, Estrogen
• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (blood)
• Breast Neoplasms (blood, drug therapy, mortality, pathology)
• Female
• Follow-Up Studies
• Humans
• Interleukin-8 (blood)
• Middle Aged
• Neoplasm Metastasis
• Prognosis
• Prospective Studies
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Survival Rate
• Time Factors