Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial

Abstract

Purpose: Exercise has been shown to improve physical and psychological conditions during cancer therapy, but mechanisms remain poorly understood. The purpose of the present study was to report the results of cancer-related biomarkers and metabolomics outcomes from the PASAPAS feasibility study. Methods: In the PASAPAS randomized controlled trial, 61 women beginning adjuvant chemotherapy for localized breast cancer were randomized in a 6-month program of weekly aerobic exercises associated with nutritional counseling versus usual care with nutritional counseling. In the present analysis of 58 women for whom blood samples were available, first, circulating levels of biomarkers (ie, insulin, insulin-like growth factor 1, estradiol, adiponectin, leptin, interleukin-6, and tumor necrosis factor α) were measured at baseline and 6-month follow-up. Changes in biomarkers were compared between exercisers (n = 40) and controls (n = 18) using mixed-effect models. Second, serum metabolites were studied using an untargeted 1H nuclear magnetic resonance spectroscopy, and orthogonal partial least squares analyses were performed to discriminate exercisers and controls at baseline and at 6 months. Results: Over the 6-month intervention, no statistically significant differences were observed between exercisers and controls regarding changes in biomarkers and metabolomic profiles. Conclusion: The present analysis of the PASAPAS feasibility trial did not reveal any improvement in circulating biomarkers nor identified metabolic signatures in exercisers versus controls during adjuvant breast cancer treatment. Larger studies preferably in women with poor physical activity level to avoid ceiling effect, testing different doses and types of exercise on additional biological pathways, could allow to clarify the mechanisms mediating beneficial effects of physical exercise during cancer treatment. Trial registration: ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1

High‐intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines

“…25,26 In line with our results, one previous study conducted by Febvey-Combeset et al found reductions in insulin, glucose, and leptin after a 6 months aerobic exercise program and nutrition counseling, as well as improvements in body composition in breast cancer patients receiving treatment. 26 In contrast, Basen-Engquist et al conducted a weight management program including diet counseling and resistance training over approximately 6 months during breast cancer chemotherapy with no differences for glucose, insulin, leptin or adiponectin compared with usual care, however the intervention group showed modest weight loss. 25 The enhanced exercise-induced effects on MetS and associated biomarkers in our study may be a result of high adherence, the high number of women with MetS at baseline, supervised in-person exercise program, and the inclusion of HIIT.…”

“…In this regard, while several studies have explored the effects of exercise on MetS associated biomarkers in breast cancer survivors, 24 only a few studies have targeted women with breast cancer undergoing chemotherapy, and have shown inconsistent results. 25,26 In line with our results, one previous study conducted by Febvey-Combeset et al found reductions in insulin, glucose, and leptin after a 6 months aerobic exercise program and nutrition counseling, as well as improvements in body composition in breast cancer patients receiving treatment. 26 In contrast, Basen-Engquist et al conducted a weight management program including diet counseling and resistance training over approximately 6 months during breast cancer chemotherapy with no differences for glucose, insulin, leptin or adiponectin compared with usual care, however the intervention group showed modest weight loss.…”

“…The present study also resulted in large improvements in biomarkers associated with MetS, such as those implicated in the regulation of glucose and lipid metabolism, as well as inflammation. In this regard, while several studies have explored the effects of exercise on MetS associated biomarkers in breast cancer survivors, 24 only a few studies have targeted women with breast cancer undergoing chemotherapy, and have shown inconsistent results 25,26 . In line with our results, one previous study conducted by Febvey‐Combeset et al found reductions in insulin, glucose, and leptin after a 6 months aerobic exercise program and nutrition counseling, as well as improvements in body composition in breast cancer patients receiving treatment 26 .…”

Clinical trial-identified inflammatory biomarkers in breast and pancreatic cancers

“…Moreover, another study focused on the effect of an anti-inflammatory diet, revealed a positive relationship between IL-6 and BMI in breast cancer patients ( 63 ). In a few of the studies reviewed here-in, there was no difference or IL-6 level change following their respective interventions ( 69 , 70 , 88 ). Other note-worthy findings relative to breast cancer did include those found by Matsumoto et al.…”

“…In addition, CA15-3, Type 1 T helper cells (Th1), C-reactive protein (CRP), and VEGF were also used in more than three studies for breast cancer for the purpose of diagnosis and treatment ( 30 , 33 , 51 , 54 , 59 , 61 , 63 , 66 , 78 , 79 ). Other biomarkers like insulin, C-C motif chemokine ligand 2 (CCL2), transforming growth factor β 1(TGF-β1), and Treg-like molecule (Treg: Regulatory T cells) were also discussed in some of our reviewed publications, regarding their relevance primarily to breast cancer treatment ( 75 , 76 , 80 , 83 , 84 , 88 , 90 ).…”