University of Oulu

Leena Tiainen, Mari Hämäläinen, Tiina Luukkaala, Minna Tanner, Outi Lahdenperä, Pia Vihinen, Arja Jukkola, Peeter Karihtala, Eeva Moilanen, Pirkko-Liisa Kellokumpu-Lehtinen, Low Plasma IL-8 Levels During Chemotherapy Are Predictive of Excellent Long-Term Survival in Metastatic Breast Cancer, Clinical Breast Cancer, Volume 19, Issue 4, 2019, Pages e522-e533, ISSN 1526-8209,

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

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Author: Tiainen, Leena1,2; Hämäläinen, Mari3; Luukkaala, Tiina4;
Organizations: 1Department of Oncology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
2Department of Oncology, Tampere University Hospital, Tampere, Finland
3The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
4Research, Development and Innovation Center, Tampere University Hospital and Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
5Department of Oncology and Radiotherapy and FICAN West Cancer Center, Turku University Central Hospital, Turku, Finland
6Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2019-10-11


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.

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Series: Clinical breast cancer
ISSN: 1526-8209
ISSN-E: 1938-0666
ISSN-L: 1526-8209
Volume: 19
Issue: 4
Pages: E522 - E533
DOI: 10.1016/j.clbc.2019.03.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Funded by the Research, Development and Innovation Center of Tampere University hospital (9U020 and 9V017) and Seppo Nieminen funds (LT, PLKL). Additional financial support was provided by Roche Inc for the plasma laboratory analysis (PLKL).
Copyright information: © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (