Exercise Rx in breast cancer care gets a boost from BREXIT

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Further support for the recommendation that exercise should be included in the treatment of women with breast cancer comes from the BREXIT randomized trial.

Results from 104 women with stage 1 to stage 3 breast cancer show that the risks of functional disability were reduced by 68% at 4 months with physical training combined with anthracycline-based chemotherapy compared to to usual care (odds ratio [OR]0.32; P = .03).

The primary endpoint score remained lower in the exercise group but was not statistically significant at 12 months (OR, 0.27; P = 0.07).

In a pre-protocol-specified analysis of women (71%) who adhered to the intervention for the full 12 months, however, “not one was functionally disabled compared to one in five usual care participants (P = 0.005),” said Stephen Foulkes, PhD, Baker Heart and Diabetes Institute, Melbourne, Australia.

The failure to show an overall difference at 12 months was likely due to increased attrition, he suggested. Five patients, four of whom were in the usual care group, could not complete the assessment at 12 months because they were functionally disabled at 4 months.

The trial focused on functional disability, defined as the maximal volume of oxygen uptake (VO2 peak) 18 ml/kg/min, as it encompasses the metabolic needs necessary to perform activities of daily living and is a strong predictor of heart failure and mortality, Foulkes explained. Importantly, approximately “one in three breast cancer survivors will fall below this threshold after completing therapy.”

The study, Posted in Traffic and presented at the recent 2022 Scientific Sessions of the American Heart Association, also aimed to determine whether exercise-based or rest-based cardiac measures predict functional disability at 12 months. The current standard of care for detecting cardiotoxicity relies on left ventricular ejection fraction (LVEF) echocardiographybut this may not be sensitive enough, given that half of heart failure patients retained LVEF.

A non-randomized pilot study by the team using exercises Cardiac MRI and cardiopulmonary exercise testing (CPET) showed that 12 weeks of exercise attenuated VO declines2 peak in breast cancer survivors receiving anthracyclines, he said. Randomized data showing lasting benefit and linking exercise to beneficial changes in cardiac function and functional disability are lacking.

Rest vs exercise test

The BREXIT trial randomly assigned 104 women to 12 months of three to four sessions per week of structured, resistance-based aerobic training or usual care lifestyle advice to be physically active during treatment, with assessments at baseline, at 4 months after completing anthracycline-based chemotherapy, and at 12 months.

As previously describedphysical training was supervised for the first 12 weeks with an intensity reduced by approximately 5% in the week following chemotherapy, followed by semi-supervised training for 14 weeks, followed by a maintenance program of 26 weeks at home or at a community health or fitness center .

Chemotherapy for all patients was four cycles of 60 mg/m2 doxorubicin combined with 600 mg/m2 cyclophosphamide. The cohort had an average age of 51 years and an average cardiorespiratory fitness of 94% of the expected rate.

VO2 the peak measured by CPET increased from baseline by 6% in the exercise group at 4 months, compared with a 13% decline in the usual care group (P = 0.003), with a gain of 8% and a loss of 7%, respectively, at 12 months (P

The overall net difference was 3.5 mL/kg/min, equivalent to an equivalent metabolic increase in fitness – an amount previously shown to have clinically significant differences in the incidence of heart failure and heart failure. cardiovascular and all-cause mortality, Foulkes said.

On cardiac MRI, changes from rest to maximal exercise (cardiac reserve) in cardiac output, stroke volume, LVEF, and right ventricular ejection fraction were also higher at 4 and 12 months in the exercise group (P

“For the first time, we have shown a relationship between changes in exercise capacity and changes in cardiac function in the setting of chemotherapy and exercise training, and that’s because we assessed the heart function during exercise,” Foulkes said.

There were small changes in both groups in resting LVEF and global longitudinal tension on echocardiography, with little differentiation between the groups. “Furthermore, we saw no correlation between changes in these measures and changes in exercise capacity over 12 months,” he said.

Physical training “leads to significant improvement in peak exercise measures of cardiac function and cardiac augmentation. And neither of these effects have been adequately characterized by current standards of care,” Foulkes concluded. .

Reached for comment, Alan H. Baik, MD, cardio-oncologist at the University of California, San Francisco, who was not involved in the study, said, “This study really supports the idea that in patients people with cancer, if they participate in a physical training program, it can really prevent functional decline and maintain their cardiovascular health in the long term.”

Nevertheless, being part of an exercise intervention for an entire year is difficult for most patients. “It’s reminiscent of cardiac rehab, that is, it’s a resource that not everyone can get and the program they had in this study was actually more intense than that provided by rehab. heart,” he said. “So I don’t know how recreable it is for most patients.”

Baik also noted that the baseline level of exercise in the trial was high, with 51% of participants meeting the guideline-recommended minimum of at least 150 minutes per week of moderate to vigorous exercise before their diagnosis. “So the concern is that this study included those who are already more open to exercise than you normally see.”

Regarding testing, Baik said that the standard resting echocardiogram is often normal in cancer patients and does not explain why their exercise tolerance is diminished, but that cardiac MRI at effort is not available in all institutions.

“I think it still makes sense to do a resting echocardiogram because we don’t want to miss an EF change or other changes that can be detected,” he said. “But it really shows that when a person’s main complaint is exercise intolerance, getting exercise testing, including CPET, could potentially be a very important part of their care.”

The authors acknowledge the potential for selection bias, but suggest that disproportionate enrollment of highly motivated volunteers and high exercise adherence should reduce the observed impact of the exercise intervention and “make the results of this study more remarkable”.

The study was funded by a grant from the World Health Organization’s Global Cancer Research Fund. The The Young Men’s Christian Association Victoria, Fitness First, Goodlife Health Clubs and the Peninsula Aquatic and Recreation Center provided in-kind support for the project. Foulkes was supported by a fellowship from the Australian Government’s Research Training Program. Baik did not report any relevant financial relationships.

Traffic. Published online November 7, 2022. Summary

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