Evaluation of metabolomic changes during neoadjuvant chemotherapy combined with bevacizumab in breast cancer using MR spectroscopy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-04

AUTHORS

Leslie R. Euceda, Tonje H. Haukaas, Guro F. Giskeødegård, Riyas Vettukattil, Jasper Engel, Laxmi Silwal-Pandit, Steinar Lundgren, Elin Borgen, Øystein Garred, Geert Postma, Lutgarde M. C. Buydens, Anne-Lise Børresen-Dale, Olav Engebraaten, Tone F. Bathen

ABSTRACT

Metabolomics investigates biochemical processes directly, potentially complementing transcriptomics and proteomics in providing insight into treatment outcome. This study aimed to use magnetic resonance (MR) spectroscopy on breast tumor tissue to explore the effect of neoadjuvant therapy on metabolic profiles, determine metabolic effects of the antiangiogenic drug bevacizumab, and investigate metabolic differences between responders and non-responders. Breast tumors from 122 patients were profiled using high resolution magic angle spinning MR spectroscopy. All patients received neoadjuvant chemotherapy, and were randomized to receive bevacizumab or not. Tumors were biopsied prior, during, and after treatment. Principal component analysis showed clear metabolic changes indicating a decline in glucose consumption and a transition to normal breast adipose tissue as an effect of chemotherapy. Partial least squares-discriminant analysis revealed metabolic differences between pathological minimal residual disease patients and pathological non-responders after treatment (accuracy of 77%, p < 0.001), but not before or during treatment. Lower glucose and higher lactate was observed in patients exhibiting a good response (≥90% tumor reduction) compared to those with no response (≤10% tumor reduction) before treatment, while the opposite was observed after treatment. Bevacizumab-receiving and chemotherapy-only patients could not be discriminated at any time point. Linear mixed-effects models revealed a significant interaction between time and bevacizumab for glutathione, indicating higher levels of this antioxidant in chemotherapy-only patients than in bevacizumab receivers after treatment. MR spectroscopy showed potential in detecting metabolic response to treatment and complementing other molecular assays for the elucidation of underlying mechanisms affecting pathological response. More... »

PAGES

37

References to SciGraph publications

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    URI

    http://scigraph.springernature.com/pub.10.1007/s11306-017-1168-0

    DOI

    http://dx.doi.org/10.1007/s11306-017-1168-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1083870351


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