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

Olivia Febvey-Combes, Elodie Jobard, Adrien Rossary, Vincent Pialoux, Aude-Marie Foucaut, Magali Morelle, Lidia Delrieu, Agnès Martin, Florence Caldefie-Chézet, Marina Touillaud, Sophie E Berthouze, Houda Boumaza, Bénédicte Elena-Herrmann, Patrick Bachmann, Olivier Trédan, Marie-Paule Vasson, Béatrice Fervers, Olivia Febvey-Combes, Elodie Jobard, Adrien Rossary, Vincent Pialoux, Aude-Marie Foucaut, Magali Morelle, Lidia Delrieu, Agnès Martin, Florence Caldefie-Chézet, Marina Touillaud, Sophie E Berthouze, Houda Boumaza, Bénédicte Elena-Herrmann, Patrick Bachmann, Olivier Trédan, Marie-Paule Vasson, Béatrice Fervers

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://ichgcp.net/clinical-trials-registry/NCT01331772?term=pasapas&rank=1.

Keywords: biomarkers; breast cancer; chemotherapy; exercise; metabolomics.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Metabolic signature (O-PLS-DA loadings) from 1H NMR serum profiles discriminating sample at 6 months of intervention with respect to baseline, for the whole cohort of exercisers and control subjects. O-PLS-DA model coefficients are provided in Table 3. Abbreviations: 3-HB, 3-hydroxybutyrate; FA, Fatty acids; VLDL, Very-low density lipoproteins.

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