Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

Lende, Tone Hoel; Austdal, Marie; Varhaugvik, Anne Elin; Skaland, Ivar; Gudlaugsson, Einar; Kvaløy, Jan Terje; Akslen, Lars A.; Søiland, Håvard; Janssen, Emiel A. M.; Baak, Jan P. A.

doi:10.21203/rs.2.11085/v3

Cited by 1 publication

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“…This paper is an explorative study based upon a recently published randomized controlled trial (RCT) approved by the Regional Ethics Committee in Western Norway (#2015/1445) and was retrospectively registered at Clinicaltrials.gov (NCT03886389). [16]. Briefly, patients in the carbohydrate group drank 200 mL pre-Op TM (Nutricia, the Netherlands) containing 12% carbohydrates, 2% glucose, and 10% polysaccharides 18 hours before surgery (i.e., the evening before surgery) and 2-4 hours before surgery (i.e., the morning of the operation day).…”

Section: Ethics Statementmentioning

confidence: 99%

“…tumor periphery) was immediately snap-frozen in liquid nitrogen and stored at -80ºC until assayed for tissue metabolomics. Before HR-MAS analysis, tissues from all of the patients were analyzed consecutively for histopathology and immunohistochemistry as described preciously [16].…”

Section: Tumor Tissue Samplingmentioning

confidence: 99%

“…In the 29 patients with available tissue, the tumors were larger (45% vs. 9% pT2/3/4, p = 0.003), had a higher histological grade (52% vs. 18% grade 3, p = 0.022), were more often ER-negative (35% vs. 3%, p = 0.002), and had higher proliferation (59% vs. 27% PPH3-positive, p = 0.002) than those without tissue. Thus, we had a selection bias of larger, non-luminal and a more proliferative tumors into the present study compared to the original study [16]. Tissue was transported on dry ice to the MR Core Facility at NTNU, Trondheim, Norway, for metabolomics analyses.…”

Section: Breast Tumor Tissue Metabolomics Analysesmentioning

confidence: 99%

“…Even though much is known about metabolism in breast cancer cells [14], little is known about the influence of carbohydrate loading in the early recovery after surgery (ERAS) program [15] on peri-operative metabolism in the systemic circulation and locally in the breast tumor. We recently conducted a randomized controlled trial (RCT) in which operable breast cancer patients were treated with either two oral loads of enriched carbohydrate solution or a standard fasting procedure comprising free drinking of tap water before surgery [16]. Among those who received oral preoperative carbohydrates, the patients with luminal breast cancer had higher tumor proliferation and adverse survival.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

Lende

Austdal

Bathen

et al. 2019

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Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Design: Explorative study. Setting: University hospital with primary and secondary care functions in south-west Norway.Interventions and Outcome Measures: 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. 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. Registration of trial: CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT03886389?cond=Breast+cancer+diet&rank=1

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Section: Ethics Statementmentioning

confidence: 99%

Section: Tumor Tissue Samplingmentioning

confidence: 99%

Section: Breast Tumor Tissue Metabolomics Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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