Effect of combined training, performed before treatment, on the transcriptomic and metabolomic profile of the tumor of women with Breast Cancer

Abstract

Tumor growth and neoadjuvant treatment induce a degradation of muscle mass and aerobic fitness in women with breast cancer. This loss in muscle mass and aerobic fitness may increase toxicity and decrease the effect of chemotherapy. Since performing strength training and aerobic training, called combined training (CT), is an effective strategy to increase muscle mass and aerobic fitness, CT should be started before chemotherapy to decrease its adverse effects. Since CT can decrease the amount of circulating glucose, it is possible to suggest that decreasing circulating glucose will alter the metabolism of the tumor, making it less able to consume glucose and then decrease its proliferation. Other mechanisms such as the expression of c-miRNAs post exercise training may contribute to decrease the aggressiveness of the tumor. Thus, investigating the clinical and molecular response of exercise training in breast cancer patients is critical. To determine the effect of HT performed in the period between breast cancer diagnosis and before the start of treatment on the following variables: a) muscle mass, b) muscle strength, c) aerobic fitness, d) physical functioning, e) quality of life, f) Ki67 levels in the tumor, g) systemic inflammatory profile, h) tumor transcriptomic profile, i) tumor metabolomic profile. Furthermore, to determine the remaining effect (after the end of treatment) of HT on the variables: a) muscle mass, b) muscle strength, c) aerobic fitness, d) physical functioning, e) quality of life, f) basal levels of c-miRNAs expression, g) systemic inflammatory profile and h) treatment toxicity and i) cancer-related fatigue. Assuming a sampling error of no more than 10%, with a confidence interval equal to 95%, a minimum sample size of 100 cases will be required. Thus, 100 women with breast cancer with an indication for neoadjuvant chemotherapy will be allocated to one of the following groups: CT before chemotherapy (CT, n=50), or control group (CG, n=50). Then, these women will perform, both before the CT period and also after, the following assessments: 1) body composition by dual-energy X-ray absorptiometry (DXA); 2) muscle strength by one repetition maximum test (1-RM); 3) aerobic fitness by direct maximal oxygen uptake test (VO2max); 4) functionality by sit and stand and Timed Up and Go tests; 05) quality of life by FACT-B questionnaire; 6) nutritional intake by food recall; 7) blood and tumor collections for molecular analyses. The same assessments of muscle mass, muscle strength, aerobic fitness, physical functioning, and quality of life, as well as the blood collections, will be done again at the end of the cancer treatment. At this time, cancer-related toxicity and fatigue analysis will also be performed. Blood samples for molecular analyses will be collected at 6 times: 1st) before the first HT session; 2nd) immediately after the first HT session; 3rd) before the last HT session; 4th) immediately after the last HT session; 5th) 3 days after the 8 weeks of HT; 6th) after the cancer treatment period. The CT will be performed 3 times a week. The TC protocol will consist of strength training (ST: 8 exercises, 1-3 sets of 8-12 RM at 80-90% of 1-RM and 2 min between sets) followed by aerobic training (3-4 sets of 3 min at 90% of VO2max by 3 min of active recovery (30% of VO2max) on cycle ergometer. If the hypotheses of this project are confirmed, patients may be directed to perform CT, prior to starting treatment, to increase muscle mass and aerobic fitness to minimize adverse effects caused by breast cancer treatment, improve response to chemotherapy, and decrease tumor aggressiveness. (AU)