Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers

Marianne E. Nome, Leslie R. Euceda, Shakila Jabeen, Julia Debik, Tone F. Bathen, Guro F. Giskeødegård, Kristin A. Taskén, Gunhild M. Mælandsmo, Bente Halvorsen, Arne Yndestad, Elin Borgen, Øystein Garred, Pål Aukrust, Thor Ueland, Olav Engebraaten, Vessela N. Kristensen, Xavier Tekpli

Research output: Contribution to journalArticle

Abstract

Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti-vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine-protein kinase erbB-2-negative breast cancers, we measured metabolites and inflammation-related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation-regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth-differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.

Original languageEnglish (US)
Pages (from-to)223-235
Number of pages13
JournalInternational Journal of Cancer
Volume146
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Neoadjuvant Therapy
Breast Neoplasms
Inflammation
Drug Therapy
Serum
von Willebrand Factor
Neoplasms
Cytokines
Growth Differentiation Factor 15
ErbB-2 Receptor
Tumor Microenvironment
Physiologic Monitoring
Bevacizumab
Nuclear Family
Vascular Endothelial Growth Factor A
Blood Proteins
Leukocytes
Randomized Controlled Trials
Biomarkers
Logistic Models

Keywords

  • bevacizumab
  • breast cancer
  • inflammation
  • metabolism
  • neoadjuvant therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. / Nome, Marianne E.; Euceda, Leslie R.; Jabeen, Shakila; Debik, Julia; Bathen, Tone F.; Giskeødegård, Guro F.; Taskén, Kristin A.; Mælandsmo, Gunhild M.; Halvorsen, Bente; Yndestad, Arne; Borgen, Elin; Garred, Øystein; Aukrust, Pål; Ueland, Thor; Engebraaten, Olav; Kristensen, Vessela N.; Tekpli, Xavier.

In: International Journal of Cancer, Vol. 146, No. 1, 01.01.2020, p. 223-235.

Research output: Contribution to journalArticle

Nome, ME, Euceda, LR, Jabeen, S, Debik, J, Bathen, TF, Giskeødegård, GF, Taskén, KA, Mælandsmo, GM, Halvorsen, B, Yndestad, A, Borgen, E, Garred, Ø, Aukrust, P, Ueland, T, Engebraaten, O, Kristensen, VN & Tekpli, X 2020, 'Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers', International Journal of Cancer, vol. 146, no. 1, pp. 223-235. https://doi.org/10.1002/ijc.32638
Nome, Marianne E. ; Euceda, Leslie R. ; Jabeen, Shakila ; Debik, Julia ; Bathen, Tone F. ; Giskeødegård, Guro F. ; Taskén, Kristin A. ; Mælandsmo, Gunhild M. ; Halvorsen, Bente ; Yndestad, Arne ; Borgen, Elin ; Garred, Øystein ; Aukrust, Pål ; Ueland, Thor ; Engebraaten, Olav ; Kristensen, Vessela N. ; Tekpli, Xavier. / Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. In: International Journal of Cancer. 2020 ; Vol. 146, No. 1. pp. 223-235.
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AU - Nome, Marianne E.

AU - Euceda, Leslie R.

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AU - Debik, Julia

AU - Bathen, Tone F.

AU - Giskeødegård, Guro F.

AU - Taskén, Kristin A.

AU - Mælandsmo, Gunhild M.

AU - Halvorsen, Bente

AU - Yndestad, Arne

AU - Borgen, Elin

AU - Garred, Øystein

AU - Aukrust, Pål

AU - Ueland, Thor

AU - Engebraaten, Olav

AU - Kristensen, Vessela N.

AU - Tekpli, Xavier

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N2 - Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti-vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine-protein kinase erbB-2-negative breast cancers, we measured metabolites and inflammation-related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation-regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth-differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.

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