Patients with breast cancer often experience a decline in cardiovascular function related to their treatment. “Treatment-induced cardiotoxicity is a major concern, and cardiovascular disease is a competing cause of death among breast cancer survivors,” said the study’s lead author, Inger Thune, MD, PhD, professor and senior consultant in oncology at Oslo University Hospital in Norway.
While there is evidence that exercise benefits survivors of breast cancer, there has been little examination of the specific types and amounts that are best undertaken during adjuvant therapy, or even whether exercise benefits patients after initial treatment, Thune said.
She and her colleagues sought to answer those questions by launching the randomized Energy Balance and Breast Cancer Aspect (EBBA)-II, first as a pilot program in 2011 and then as a study in 2014. The primary intervention ended about a week before the symposium, held Dec. 4-8, 2018.
The study tested a 12-month strength and endurance training program in which 271 women participated during adjuvant treatment, with the goal of determining whether it improved cardiopulmonary function. Other endpoints were to evaluate the program’s safety and to determine the recommended type, dose, intensity, and duration of exercise for this population. Members of a control group (n = 274) participated in exercise at their own discretion, with no restrictions, according to current clinical guidelines in Norway.
Women in the supervised exercise group began the program 3 weeks after surgery and were put into groups of 10 to 12 for training led by physiotherapists. Together, the groups spent 2 hours a week doing moderate- to high-intensity aerobic exercise, stretching, and weight-bearing activities outdoors. Members were also asked to complete 120 minutes per week of exercise at home. Exercise was tailored for individual patients based on their cardiovascular status.
The program ended 12 months after surgery, and the women are being followed for 10 years.
Participants were selected and informed about the program at diagnosis by trained nurses at 3 outpatient clinics; if they were interested in participating, the patients were invited by physicians via telephone. Their cardiovascular capacity was assessed using the same protocol across the board, with VO2 max (maximal oxygen uptake, a common measure of cardiovascular fitness) checked before surgery, at 6 months, and at 12 months.
The women, whose mean age was 55, were fairly healthy besides having early-stage breast cancer. They had no known severe comorbidities, no previous cancer history, and were capable of participating in exercise. Most had stage II invasive breast carcinoma of no special type that was estrogen receptor-positive.
The educational status, body mass index and disease characteristics of participants in the 2 groups were very closely matched. In addition, most of the women had undergone surgery, and similar percentages were undergoing chemotherapy (approximately 55%), radiation (over 75%), and hormone treatment (nearly 60%). Some patients did not undergo any treatment after surgery.
As for cardiovascular fitness, the mean baseline VO2 max was 31 ml/kg/min in the intervention group and 31.7 ml/kg/min in the control group.
An evaluation of all participants showed that cardiovascular function declined in the 6 months after treatment and then rose again. In the supervised exercise group, VO2 max dropped 2.7% below baseline at 6 months and then rose to 0.3% above baseline at 12 months. In the standard care group, VO2 max was down 10% at 6 months and rose to 8.9% below baseline at 12 months.
Strictly in patients who had not undergone chemotherapy (n = 242), participants in the intervention group saw an increase in their VO2 max at 6 months and ended up with a 1.6% gain over baseline at 12 months. VO2 max in control group members who had never taken chemotherapy had dropped at 6 months and declined even more — by 2.7% — at 12 months.
Among those who did receive chemotherapy (n = 295), members of the intervention group experienced a drop in cardiac function of 0.8% at 12 months, compared with a 6.4% decrease for those in the control group. Among patients who took taxanes, supervised exercise patients experienced a 1.4% decrease in their VO2 max at 12 months, compared with a 7.3% decrease for standard-care patients at that time point.
There was a 70% adherence rate among study participants.
Thune said the study had met its primary goal of determining whether the exercise program improved pulmonary function. While all study participants benefited from exercise during adjuvant treatment, she said, “our study supports incorporation of supervised clinical exercise programs into breast cancer treatment guidelines.”
In the future, Thune said, patients with breast cancer who are undergoing adjuvant chemotherapy should be offered tailored exercise programs based on their assessed pretreatment levels of physical function. Aside from the cardiovascular benefits measured in her study, she noted, exercise may also help reduce fatigue and improve quality of life.
Future studies will explore the effects of exercise on the risk of breast cancer recurrence, metastasis, metabolic profile, and ability to work, Thune said.
“Patients should discuss their plans with their doctor(s), but in general, our study supports incorporation of supervised clinical exercise programs into breast cancer treatment guidelines,” she said. The researchers believe their study is the largest to date to have checked cardiovascular function prior to any type of breast cancer treatment. The variability of exercise frequency and intensity in the control arm may represent a limitation of the study, Thune said.
The study was sponsored by the Norwegian Research Council, Norwegian Health Authority, Oslo University Hospital, St. Olavs Hospital, and Active Against Cancer — Gjensidige Foundation.
Thune I, Husøy A, Frydenberg H, et al., Cardiovascular function and the effect of exercise training during adjuvant breast cancer treatment. Results from the EBBA-II trial (NBCG-14). Presented at: 2018 San Antonio Breast Cancer Symposium (SABCS); Dec. 4-8, 2018; San Antonio, Texas.
This article as originally published on OncLive® as “Exercise Helps Women Maintain Cardiovascular Function During Adjuvant Breast Cancer Treatment.”