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Clin Breast Cancer. 2019 Aug;19(4):e522-e533. doi: 10.1016/j.clbc.2019.03.006. Epub 2019 Apr 4.

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

Author information

1
Department of Oncology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland. Electronic address: leena.tiainen@tuni.fi.
2
The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
3
Research, Development and Innovation Center, Tampere University Hospital and Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.
4
Department of Oncology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland.
5
Department of Oncology and Radiotherapy and FICAN West Cancer Center, Turku University Central Hospital, Turku, Finland.
6
Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.

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.

KEYWORDS:

Bevacizumab; First-line chemotherapy treatment; Interleukin 8; Metastatic breast cancer; Prognosis

PMID:
31029558
DOI:
10.1016/j.clbc.2019.03.006
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