In this proof-of-concept single-arm study, we examined the effectiveness of a flexible exercise program, consisting of 24 sessions of combined exercise training with a targeted frequency of 2 sessions per week, on cardiovascular fitness and strength in a group of biological females with recently diagnosed breast cancer. We expanded the length of the program as needed to accommodate participants’ medical appointments and treatment-related side-effects. Participants completed the exercise intervention over a median of 20 weeks, and attended training sessions at a median frequency of 1.2 sessions per week. Although this frequency was lower than targeted, our study demonstrated that exercising < 2 times per week was sufficient to stimulate significant cardiovascular fitness and strength adaptations. Further, our intervention may have prevented the anticipated development of deleterious treatment-related changes to body composition and metabolism. These findings form the foundation for future, larger-scale pragmatic studies in which we will further explore this hypothesis.
Cardiovascular fitness and strength improved despite the low frequency of exercise training sessions. Although we prescribed a total of 24 exercise sessions at a targeted frequency of 2 sessions per week, participants only attended a median of 1.2 exercise sessions per week over 20 weeks. No participants completed the study within in the targeted time frame of 12 weeks. The median frequency of 1.2 sessions per week was lower than current expert panel recommendations for individuals undergoing active treatment for cancer (aerobic exercise 3 times per week plus resistance exercise 2 times per week) [9]. Despite that our participants did not meet these recommendations, our intervention may have been sufficient to stimulate significant improvements in cardiovascular fitness, blood pressure, and strength. These improvements are particularly important, considering that VO2peak and grip strength are inversely correlated with cancer-specific and all-cause mortality [22, 23]. Future work should investigate whether behavioural supports (e.g., physical activity and/or diet counselling) may improve adherence to recommendations.
Previous work has shown that predicted VO2peak decreases by 10–33% in breast cancer patients during 12–16 weeks of chemotherapy [24, 25]. Chemotherapy treatment is also associated with decrements of 5–9% in upper and lower body isometric force production [24]. Our exercise intervention not only prevented these expected decreases in physical fitness but resulted in significant improvements in resting blood pressure, final-stage workrate during a graded exercise test, and predicted VO2peak. We also observed significant increases in right biceps and left and right quadriceps isometric strength. Left biceps strength did not increase, however, this is likely because 33/52 (63%) participants had cancer in their left breast and may have been unable or hesitant to lift heavier loads post-surgery or during ongoing localized radiation treatment. Future studies that include a usual care group are needed to confirm our findings. Nevertheless, it is likely that these improvements in fitness are attributable to our exercise intervention since participants were instructed not to participate in any other structured exercise program for the duration of this study. Considering that breast cancer patients tend to lose strength during treatment, the maintenance of left arm strength and improvements in cardiovascular fitness and blood pressure outcomes indicate a beneficial physiological response to exercise training in individuals undergoing treatment for breast cancer.
Body composition and markers of glucose and lipid regulation were maintained during the study.
Fasting concentrations of glucose, insulin, cholesterols, and triacylglycerides were maintained over the course of exercise training. Numerous studies have reported significant deleterious perturbations to glucose [5, 26, 27] and lipid [5, 28, 29] metabolism during adjuvant treatment for breast cancer. Specifically, fasting serum glucose [5] and insulin [5, 26, 27] concentrations have been shown to increase by ~ 20% and ~ 20–75%, respectively, within the first 6 months following diagnosis. Unhealthy lipid partitioning [5, 26, 28] (increased LDL-c and TAG concentrations, and/or decreased HDL-c concentrations) has also been observed early in the treatment trajectory. Consistent with these findings, Dieli-Conwright et al. [5] observed that 72.5% of newly diagnosed participants developed metabolic syndrome (a cluster of characteristics that increases the risk for type 2 diabetes and cardiovascular disease) after 12–18 weeks of adjuvant chemotherapy. The authors also observed significant treatment-related increases in all 5 components of metabolic syndrome (waist circumference, resting blood pressure, and fasting blood glucose, TAG, and HDL-c concentrations). Conversely, in the present study, we observed that metabolic outcomes did not worsen during treatment, likely a result of our exercise intervention.
Although metabolic health and body composition were maintained in our cohort of participants, several potential mechanisms may have prevented our capacity to detect exercise-mediated improvements in these outcomes. Participants exercised at a frequency lower than what has previously been demonstrated to elicit losses in fat mass during treatment (1.2 vs. 3 sessions per week) [12]. But, given that the most common reasons for missed or rescheduled sessions were treatment-related illness and medical appointments, the exercise frequency observed in our intervention may be more realistic of patients early in the treatment trajectory. Individuals with newly diagnosed breast cancer also experience elevated stress and anxiety [20], which can further inhibit motivation to initiate and adhere to an exercise program [21]. As such, our findings are important towards understanding how flexible exercise programs may impact outcomes of interest, like fitness, body composition, and metabolism, outside of controlled research studies (i.e., in the “real world”). Despite that participants exercised at a lower frequency (median of 1.2 sessions per week), glucose and lipid outcomes did not worsen. Perhaps the addition of a concurrent nutrition intervention to manage energy, fat, and protein intake would have supported improvements in markers of glucose and lipid metabolism. In future, a larger-scale study that includes a usual care group would confirm that these changes are specifically attributable to the exercise intervention. Our smaller-scale findings are promising: if harmful metabolic and body composition changes can be prevented during treatment, rather than corrected later in treatment or in survivorship, breast cancer patients who enter survivorship may be at a reduced risk of developing secondary conditions, such as type 2 diabetes, cardiovascular disease, or even cancer recurrence.
There are several limitations to the present study. Firstly, we recruited a relatively heterogeneous group of participants: any female ≥ 18 years with stage I-IIIB breast cancer, regardless of menopausal status or treatment type, was eligible to participate. Second, our lack of a usual care reference group may have limited our ability to detect true longitudinal changes in our intervention group (and between-group differences in body composition and metabolism). However, this study was hypothesis-generating and builds the foundation for our future work, which will test the effect of a flexible exercise program on fitness, body composition, and metabolic health during treatment for breast cancer using a randomized controlled design.
In summary, we observed that 1.2 sessions per week of combined aerobic and strength training significantly improved cardiovascular fitness and strength in a group of females with newly diagnosed breast cancer. Further, body composition and features of glucose and lipid metabolism did not worsen over the course of treatment, possibly as a result of exercise training. This is the first study to allow participants unlimited time to complete a fixed number of sessions, as a pragmatic means of accommodating cancer-specific barriers to exercise. This approach may improve the generalizability of our findings. Future larger-scale studies that include a usual care group are needed to confirm this preliminary study.