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Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers
Author(s) -
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
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32638
Subject(s) - bevacizumab , medicine , chemotherapy , inflammation , breast cancer , oncology , neoadjuvant therapy , cancer
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.