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Exercise During Adjuvant Therapy Improves Cardiac Function

Bennett, Christina, MS

doi: 10.1097/01.COT.0000553543.22371.44
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SAN ANTONIO—Breast cancer patients who participated in an exercise program during adjuvant therapy had better cardiac function than patients who did not, according to data from the EBBA (Energy Balance and Breast cancer Aspects)-II randomized controlled trial presented at the 2018 San Antonio Breast Cancer Symposium (Abstract GS5-02).

Studies have shown that breast cancer patients not only have a higher risk of cardiovascular disease, but also a higher risk of dying from cardiovascular disease than the general population (Breast Cancer Res Treat 2018;170(1):119-127). The findings suggest that exercise programs could be used to counteract the harmful effects of adjuvant therapy on cardiac function.

“Even Hippocrates said that walking is the man's best medicine,” said study presenter Inger Thune, MD, PhD, Professor and senior consultant in oncology, Oslo University Hospital, Norway. She went on to cite Italian physician Bernardino Ramazzini, who prescribed exercise as well as rest and a walk in the fresh air.

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EBBA-II Clinical Trial

The EBBA-II trial (NCT02240836) enrolled adult women with stage I or II breast cancer or with ductal carcinoma in situ grade 3. Patients were ineligible for trial enrollment if they had heart disease, uncontrolled diabetes, or a body mass index greater than 40 kg/m2.

Study participants were randomly assigned to either the control arm or intervention arm after surgery. Participants in the intervention arm joined a 12-month tailored exercise program based on their ventilatory maximal oxygen consumption (VO2max) at baseline. VO2max is a measure of cardiovascular fitness.

As part of the program, participants met for supervised group training sessions for 60 minutes twice a week for 12 months and were instructed to exercise for 120 minutes each week on their own at home. In total, participants in the intervention arm exercised for a total of 240 minutes each week. Participants in the control arm were instructed to follow a standard of care regimen according to the Norwegian Breast Cancer Group guidelines.

Participants had to complete a cardiopulmonary exercise test before surgery, 6 months on the exercise program or standard care, and 12 months on the exercise program or standard care. The test involved exercising on a treadmill until exhaustion and assessment of various measurements, such as VO2max. The primary outcome was change in VO2max between baseline and 12 months on study.

A total of 545 participants were randomized to either the control or intervention arm. Only 9.2 percent of participants withdrew from study after randomization, leaving 258 in the control arm and 237 in the intervention arm.

The study population had a mean age at diagnosis of 55 years, a mean body mass index of 25.6 kg/m2, and a mean VO2max before surgery of approximately 31 mL/min/kg. Participants had a mean tumor diameter of approximately 17 mm, and approximately 22 percent of participants had lymph node metastasis. Most participants had estrogen-positive disease (88% in the intervention arm and 87% in the control arm) and progesterone receptor-positive disease (72% in the intervention arm and 68% in the control arm). Approximately 13 percent of participants had HER2-positive disease.

Most participants underwent breast-conserving surgery (69% in the intervention arm and 74% in the control arm) and had sentinel node examination (85% in the intervention arm and 86% in the control arm); approximately 12 percent of participants underwent axillary dissection. Fifty-five percent of participants received a form of chemotherapy, either anthracycline or taxanes; most received radiation therapy (77% in the intervention arm and 85% in the control arm); and most received endocrine therapy (60% in the intervention arm and 56% in the control arm).

“None of these differences were significantly different in these two groups,” Thune said about the patient and tumor characteristics.

As for adverse events during the exercise program, Thune said they “didn't see much of that at all.” Some patients reported fatigue while on chemotherapy or during the cardiopulmonary exercise test and one participant had an injured shoulder.

At 6 months, all study participants had a decline in VO2max. At 12 months, however, participants on the exercise program had an average improvement of 0.3 percent in VO2max, whereas participants on standard of care had an average decline of 8.9 percent in VO2max.

A subgroup analysis revealed that, among participants who did not receive chemotherapy, those on the exercise program had an average improvement of 1.6 percent in VO2max at 12 months and those on standard of care had an average decline of 2.7 percent. Among participants who received chemotherapy, those on the exercise program had an average decline of 0.8 percent in VO2max and those on standard of care had an average decline of 6.4 percent. Among participants who received a taxane, those on the exercise program had an average decline of 1.4 percent in VO2max and those on standard of care had an average decline of 7.3 percent.

Adherence to the full 12 months of exercise intervention program was 70 percent, which Thune described as “high.”

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Study Findings

“The EBBA-II trial met its primary endpoint in the exercise group,” concluded Thune. “All subgroups of patients benefitted from physical activity during breast cancer treatment, and our study supports incorporation of supervised and safe clinical exercise program into breast cancer treatment guidelines.

“Breast cancer patients receiving chemotherapy should be offered [a] tailored exercise program based on assessed pretreatment level of physical function.”

Eleni Andreopoulou, MD, breast oncologist at Weill Cornell Medicine and NewYork-Presbyterian, talked to Oncology Times about the study. She noted that the risk for cardiotoxicity is “one of the biggest challenges” for breast oncologists and that the goal of curing patients in the adjuvant setting could be “jeopardized” by the risk of cardiotoxicity.

She described the study as “a very significant report” on how exercise could improve cardiovascular function and also lay the groundwork for preventing cardiotoxicity. The study is a “confirmation” that an exercise program tailored to each patient's needs will be important alongside conventional systemic treatment to prevent disease relapse and improve overall outcomes, she said.

Christina Bennett is a contributing writer.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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