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Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study.

Abstract：

BACKGROUND: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. TRIAL OF REGISTRATION:ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Lende 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

doi

10.1186/s12885-019-6393-7

subject

Has Abstract

pub_date

2019-12-04 00:00:00

pages

1183

issue

issn

1471-2407

pii

10.1186/s12885-019-6393-7

journal_volume

pub_type

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Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study.