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 southwest 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 preoperative 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.

Ferroptosis‐related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma

“…And the results revealed overexpression of CHAC1 significantly inhibited cell proliferation and induced cell death, but cast limited influence on the abilities of cell migration and invasion. It is reported dysregulated GSH metabolism widely exist in malignant tumours 28‐30 . And Heike Miess has demonstrated that higher levels of GSH were detected in higher malignancy and later stage of KIRC 10 .…”

“How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question

“…A recent prospective long-term breast cancer study found that perioperative high intake of glucose was not only associated with high insulin blood levels but also with an extremely poor prognosis ( 34 ). This finding could be further correlated with significant metabolomics changes in the blood shortly after the operation ( 35 ). A prospective glucose intervention study, or intervention with medicines which can reduce insulin blood levels in stage IV NSCLC patients, therefore would be interesting.…”

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

“…Some have hypothesized that growth factor stimulation in response to intraoperative tissue damage, can increase HER2 receptor activation in incompletely resected pre-invasive breast cancer thus increasing risk for tumor cell proliferation and spread (141). Procedures that might elevate blood glucose or insulin levels should be avoided, as glucose is known to accelerate breast cancer development (142)(143)(144)(145)(146)(147). Products used in anesthesia might also increase blood glucose and insulin levels (148).…”

“…KMT should decrease the need for dexamethasone pretreatment, a problematic therapy that can inadvertently increase availability of glucose to the tumor cells while also inhibiting chemotherapyinduced apoptosis (192)(193)(194). It is well-known that glucose and hyperglycemia contribute to rapid breast cancer growth (146,195,196). Consequently, KMT could reduce inflammation and glucose systemically, thus enhancing the anti-tumorigenic properties of the microenvironment.…”