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dc.contributor.authorLende, Tone Hoelen_US
dc.contributor.authorAustdal, Marieen_US
dc.contributor.authorBathen, Tone Frosten_US
dc.contributor.authorVarhaugvik, Anne Elinen_US
dc.contributor.authorSkaland, Ivaren_US
dc.contributor.authorGudlaugsson, Einaren_US
dc.contributor.authorEgeland, Nina Granen_US
dc.contributor.authorLunde, Sirien_US
dc.contributor.authorAkslen, Lars A.en_US
dc.contributor.authorJonsdottir, Kristinen_US
dc.contributor.authorJanssen, Emielen_US
dc.contributor.authorSøiland, Håvarden_US
dc.contributor.authorBaak, Jan P.A.en_US
dc.PublishedLende TH, Austdal M, Bathen TF, Varhaugvik AE, Skaland I, Gudlaugsson E, Egeland NG, Lunde S, Akslen LA, Jonsdottir K, Janssen EAM, Søiland H, Baak JPA. Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study. BMC Cancer. 2019;19(1):1183eng
dc.description.abstractBackground: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods: The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results: Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions: Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients.en_US
dc.rightsAttribution CC BYeng
dc.subjectBreast cancereng
dc.subjectCarbohydrate loadeng
dc.subjectInsulin c-peptideeng
dc.subjectTumor glutathioneeng
dc.subjectFasting stateeng
dc.subjectKetonic bodieseng
dc.subjectClinical outcomeeng
dc.titleMetabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative studyen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Authors
dc.source.journalBMC Cancer

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