Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients \u2500 a randomized trial

Abstract

BackgroundConflicting results have been reported on the influence of carbohydrates in breast cancer.ObjectiveTo determine the influence of pre-operative per-oral carbohydrate load on proliferation in breast tumors.DesignRandomized controlled trial.SettingUniversity hospital with primary and secondary care functions in South-West Norway.PatientsSixty-one patients with operable breast cancer from a population-based cohort.InterventionPer-oral carbohydrate load (preOp™) 18 and 2–4 h before surgery (n = 26) or standard pre-operative fasting with free consumption of tap water (n = 35).MeasurementsThe primary outcome was post-operative tumor proliferation measured by the mitotic activity index (MAI). The secondary outcomes were changes in the levels of serum insulin, insulin-c-peptide, glucose, IGF-1, and IGFBP3; patients’ well-being, and clinical outcome over a median follow-up of 88 months (range 33–97 months).ResultsIn the estrogen receptor (ER) positive subgroup (n = 50), high proliferation (MAI ≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p = 0.038). The CH group was more frequently progesterone receptor (PR) negative (p = 0.014). The CH group had a significant increase in insulin (+ 24.31 mIE/L, 95% CI 15.34 mIE/L to 33.27 mIE/L) and insulin c-peptide (+ 1.39 nM, 95% CI 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (− 0.26 nM; 95% CI − 0.46 nM to − 0.051 nM) compared to the fasting group. CH-intervention ER-positive patients had poorer relapse-free survival (73%) than the fasting group (100%; p = 0.012; HR = 9.3, 95% CI, 1.1 to 77.7). In the ER-positive patients, only tumor size (p = 0.021; HR = 6.07, 95% CI 1.31 to 28.03) and the CH/fasting subgrouping (p = 0.040; HR = 9.30, 95% CI 1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with relapse-free survival of 100% in the fasting group vs. 33% in the CH group (p = 0.015; HR = inf). The CH group reported less pain on days 5 and 6 than the control group (p < 0.001) but otherwise exhibited no factors related to well-being.LimitationOnly applicable to T2 tumors in patients with ER-positive breast cancer.ConclusionsPre-operative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2 patients.Trial registrationCliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.