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Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study.

ABSTRACT: BACKGROUND:With increasing number of breast cancer survivors, more attention is drawn to long-term consequences of curative cancer treatment. Adjuvant treatment of breast cancer patients is associated with several unfavorable medical conditions, including dyslipidemia, insulin resistance, and obesity, potentially leading to cardiovascular disease and/or the metabolic syndrome. The aim of this explorative study is to investigate metabolic side effects of adjuvant treatment in breast cancer patients. METHODS:A cohort of 13 premenopausal and 20 postmenopausal women with early stage breast cancer were extensively examined prior to, immediately after and 1 year after ended adjuvant chemotherapy and compared with healthy controls (N?=?36) matched by age and menopausal status. Repeated examinations included: anthropometric measures, DEXA scans, 24-h blood pressure measurements, and blood samples [high sensitivity CRP, lipid profile and glucose metabolism, including homeostatic model assessment (HOMA)]. RESULTS:At baseline, breast cancer patients were similar to healthy controls regarding all measures. From baseline to 1-year post-treatment specific components of the metabolic syndrome increased significantly in premenopausal breast cancer patients; body fat (P?=?0.01), triglycerides (P?=?0.03), waist circumference (P?=?0.008) and diastolic blood pressure (P?=?0.04). In postmenopausal patients, waist circumference also increased significantly (P?=?0.03), and High density lipoprotein (HDL) cholesterol decreased significantly (P?=?0.05). CONCLUSIONS:Specific components of the metabolic syndrome changed significantly during chemotherapy in early stage breast cancer patients. After 1 year, several key parameters remained pathologically changed. Premenopausal breast cancer patients seemed to be especially prone to develop these unfavorable changes. Trial registration ClinicalTrial.gov, registration number NCT02652975. Registered 15 December 2015-Retrospectively registered, https://clinicaltrials.gov/ .

SUBMITTER: Fredslund SO

PROVIDER: S-EPMC6444586 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study.

Fredslund Stine Overvad SO Gravholt Claus Højbjerg CH Laursen Britt Elmedal BE Jensen Anders Bonde AB

Journal of translational medicine 20190401 1

<h4>Background</h4>With increasing number of breast cancer survivors, more attention is drawn to long-term consequences of curative cancer treatment. Adjuvant treatment of breast cancer patients is associated with several unfavorable medical conditions, including dyslipidemia, insulin resistance, and obesity, potentially leading to cardiovascular disease and/or the metabolic syndrome. The aim of this explorative study is to investigate metabolic side effects of adjuvant treatment in breast cance ...[more]

PMID: 30935397

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Project description:BackgroundThe 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.MethodsThe 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.ResultsFourteen 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.ConclusionsPreoperative 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 registrationClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

Project description:BackgroundWeight gain often occurs after breast cancer (BC) diagnosis and obesity along with sedentary behavior are associated with increased risk of BC recurrence and mortality. The primary objective of this study was to determine whether a significant weight loss, of approximately 10%, would lead to beneficial changes in biomarkers associated with cancer and/or cancer recurrence, and quality of life (QOL) in overweight and obese BC survivors.MethodsThis parallel-arm study took place in Minneapolis, Minnesota, from January 2009 until March 2010. Participants were overweight and obese postmenopausal BC survivors who had completed treatment at least 3 months prior to enrollment and who did not smoke. Twenty-one BC survivors were randomized, via a random number generator computer software, to a 1000-calorie deficit feeding and exercise intervention (CR) or a weight management counseling intervention (WM) for 12 weeks followed by a 6-week follow-up. Body weight, biomarkers, and QOL were measured at baseline, weeks 6, 12, and 18. Body composition and fitness level were measured at only two time points.ResultsTwenty-one women were enrolled into the study and 20 completed all time points. Weight loss occurred with both interventions. Body weight in CR changed from 85.5 (95% confidence interval (CI) 77, 94) kg to 76.7 (95% CI 68.1, 85.2) kg, whereas in WM it changed from 98.3 (95% CI 89.8, 106.8) kg to 93.2 (95% CI 84.6, 101.7) kg. Fitness in CR changed from 4.9 (95% CI 4, 5.8) to 6.3 (95% CI 5.4, 7.2). CR led to lower plasma levels of leptin, F2-isoprostanes, and CRP. Quality of life seemed to improve with both interventions, while sleep quality decreased only in CR.ConclusionsOverweight and obese BC survivors were able to adhere to a strict diet and exercise program, which significantly decreased body weight, increased fitness level, and improved biomarkers and QOL. However, the strict dietary intervention in CR seemed to decrease participants' sleep quality and social relationships. Future larger randomized controlled trials should focus on behavioral modification and personalized nutrition counseling to help breast cancer survivors achieve a sustainable weight loss and fitness level.Trial registrationClinicalTrials.gov identifier: NCT02940470.

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Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study.

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Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study.

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