To our knowledge, only one other study has examined the predictors of exercise adherence during breast cancer chemotherapy []. Numerous studies have examined the cross-sectional correlates of exercise participation in breast cancer survivors, usually focusing on social cognitive variables and long term breast cancer survivors [-]. Moreover, several studies have examined the prospective correlates of exercise participation in breast cancer survivors [,] or the predictors of adherence to a prescribed exercise program in long term breast cancer survivors [,]. The determinants of exercise adherence during breast cancer chemotherapy may be quite different than during survivorship because of the known toxicities of these treatments. Moreover, none of these previous studies have examined adherence to different types and doses of exercise.
Overall adherence to supervised exercise in the CARE trial was 73%. In our START trial involving breast cancer patients receiving chemotherapy, adherence to the aerobic exercise and resistance exercise interventions was about 70% each []. Adherence to the STAN intervention in the CARE Trial, which is comparable to the aerobic exercise intervention in the START Trial, was 78% suggesting slightly better adherence in CARE despite the more difficult chemotherapy treatments containing taxanes. These adherence rates are within the range reported for other trials of exercise during cancer treatments []. Nevertheless, adherence in the CARE Trial was still not optimal and a better understanding of the determinants of adherence may inform behavior support interventions.
The strongest predictor of exercise adherence in the CARE Trial was the location/center at which the exercise was performed with Vancouver participants achieving higher adherence than Edmonton or Ottawa participants. We previously reported the same finding in our START Trial and offered several possible explanations []. One explanation was that Vancouver participants may have received more personal attention because the fitness center in Vancouver was only training CARE Trial participants whereas the Edmonton fitness center was training participants from multiple trials and the Ottawa fitness center was open to staff and patients not participating in clinical trials. This focus on breast cancer patients in Vancouver may have provided the women with more one-on-one attention to address individual needs. Moreover, we made a similar observation in our Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial where we observed higher adherence to supervised exercise in Edmonton than Calgary []. We noted that the Edmonton training facility was exclusively for clinical trial participants whereas the Calgary training facility was a community-based facility open to the public []. Other possible explanations for site differences include: (a) the more moderate climate in Vancouver compared to harsher winters in Edmonton and Ottawa, (b) possible demographic differences in each city, (c) different referral patterns at each cancer center, and (d) travel time and convenience of accessing each fitness center. Future multicenter exercise trials should continue to report on adherence differences across sites.
Our trial also demonstrated that adherence to the STAN intervention was better than for the two higher dose exercise interventions. In some ways, this finding is not surprising given the many side effects of chemotherapy that may influence the amount of exercise completed during chemotherapy [,]. Nevertheless, it is unclear why doing more exercise during an exercise session (double the duration) would have an impact on the number of exercise sessions attended (frequency); especially given that fitness trainers instructed patients to complete only as much exercise as they were willing and able to do each session. One possible explanation is that when breast cancer patients were making a judgment about whether to attend their exercise session, they were factoring in the amount of time and/or anticipated difficulty of the session. Patients experiencing some fatigue, pain, hot flashes, nausea, or other symptoms that occurred during chemotherapy (i.e., after our baseline assessment of symptoms) might have felt that a 25–30 minute exercise session would be tolerable but not a 50–60 minute aerobic or combined exercise session. Moreover, patients with busy lives and additional medical appointments might have felt that a 25–30 minute exercise session was more feasible than a 50–60 minute session. Based on our clinical observations, it is possible that 50–60 minutes of aerobic or combined exercise may be close to the “maximum tolerated dose” of exercise for breast cancer patients receiving current chemotherapy protocols.
Interestingly, the CARE trial showed that endocrine symptoms (e.g., hot flashes, night sweats) at baseline were negative predictors of exercise adherence in breast cancer patients. To our knowledge, the CARE trial is the first to report this association. It seems intuitive that these types of symptoms may interfere with a patient’s ability and willingness to engage in exercise during chemotherapy. Nevertheless, the primary results of the CARE Trial actually showed that the higher dose exercise interventions were superior to STAN for managing endocrine symptoms []. Consequently, strategies to help breast cancer patients maintain exercise while experiencing such symptoms are needed (e.g., removing wigs, lighter clothing, cooler environments, personal fans).
Our trial also showed that exercise adherence during chemotherapy is predicted by the length of the chemotherapy protocol. Again, to our knowledge, the CARE Trial is the first to report that the length of the chemotherapy protocol may influence exercise adherence. It is well-known that the adverse effects of chemotherapy accumulate over the course of each cycle, and these accumulating side effects may interfere with exercise adherence [,]. Nevertheless, it is also possible that the lower adherence rate during longer chemotherapy protocols may simply reflect the difficulty of adhering to a longer exercise program. Unfortunately, we did not collect data on any toxicities during chemotherapy which might have directly informed this question. Consequently, these data only indirectly support the idea that chemotherapy toxicity may be the driving factor behind poorer exercise adherence to longer chemotherapy protocols. Regardless, additional support for patients on longer and/or more toxic chemotherapy protocols may be needed.
Patients with higher aerobic fitness and fewer functional problems also achieved better adherence. We observed the same finding in the START Trial []. It is possible that a minimum fitness level is needed to allow breast cancer patients to tolerate and respond to exercise training during chemotherapy. Future trials should determine if very unfit women can benefit from exercise during chemotherapy or whether it may be more prudent to initiate exercise in these women after adjuvant therapies are completed. In our paper reporting the sleep outcomes from the CARE Trial [], we found that only higher fit breast cancer patients benefitted from the higher dose exercise interventions. The fact that baseline aerobic fitness is a predictor of exercise adherence is a dilemma for exercise researchers. Demonstrating the benefits of an exercise intervention is a precarious balance between enrolling participants who are most likely to benefit (i.e., generally those who are least fit) and enrolling participants who are most likely to adhere (i.e., generally those who are more fit).
We also identified two interesting interactions between the predictors and group assignment suggesting that different exercise interventions during chemotherapy may have different determinants of adherence. For body mass index, healthy weight patients adhered equally well to all three exercise interventions whereas overweight patients adhered best to STAN and worst to COMB; and obese patients adhered best to STAN and worst to HIGH. These data suggest that overweight and obese patients may struggle with higher dose exercise interventions. Several large studies have reported that higher body mass index is associated with lower exercise in cancer survivors [-]. Given that body mass index is one of the most consistent predictors of exercise adherence in cancer survivors, interventions targeting obese cancer survivors may be warranted, especially if higher dose exercise interventions are being contemplated.
For disease stage, patients with localized disease (stage I/IIa) adhered equally well to all three exercise interventions whereas patients with regional disease (stage IIb/III) adhered better to the STAN intervention than the two higher dose exercise interventions. In cross-sectional studies, the role of disease stage has been mixed with Irwin et al. [] reporting a positive association between disease stage and exercise levels, Hong et al. [] reporting a small negative association, and Milne et al. [] reporting no association. In the START trial, we found that patients with more advanced disease achieved better adherence. The CARE Trial data are consistent with the START data showing that the more advanced stage patients had slightly better adherence to the STAN intervention (see Figure 2) which was comparable to the aerobic exercise intervention in START. However, the CARE Trial data show that these higher disease stage patients struggled with the higher dose exercise interventions.
It is important to briefly note the many variables in our study that did not predict exercise adherence either in univariate or multivariate analyses. Variables that predicted exercise adherence in univariate but not multivariate analyses included baseline aerobic exercise, comorbidities, FEC-D chemotherapy, peak rating of perceived exertion, peak respiratory exchange ratio, leg strength, lean body mass,% body fat, physical well-being, and peripheral neuropathy symptoms. These variables may have relevance for exercise adherence and should be considered in future research. Variables that did not predict adherence, even in univariate analyses, included all demographic factors (i.e., age, marital status, education, income, and ethnicity); type of surgery or receipt of taxanes, anthracyclines, or Herceptin; and the patient-reported outcomes of physical functioning, fatigue, and breast cancer symptoms.
The strengths of our study include being the first study to prospectively examine the predictors of different types and doses of supervised exercise in breast cancer patients receiving chemotherapy, the assessment of many different potential predictors, the use of an objective measure of exercise adherence, the detailed cancer data that allowed us to examine the impact of several important chemotherapy variables, and the large sample size that allowed us to examine potential interactions between the predictors and the exercise interventions. One limitation of our study is the failure to examine predictors of long term exercise maintenance after a structured exercise program. We have previously reported predictors of exercise six months after supervised exercise during chemotherapy in breast cancer [] and lymphoma patients []. In the CARE Trial, we will have data at six months, 1 year, and 2 years to examine this issue. Another limitation is that our predictors explained only 26% of the variance in exercise adherence, suggesting that other important factors may affect adherence. Some likely prospects include treatment toxicities and unexpected family events that occur after randomization which would require prospectively collecting such data. Finally, we conducted many statistical analyses which raises the possibility that some of the associations may be due to chance.
In summary, we examined predictors of adherence to three different exercise interventions in breast cancer patients receiving chemotherapy. Higher exercise adherence was achieved by breast cancer patients in Vancouver, with fewer endocrine symptoms, randomized to STAN, with fewer exercise limitations, receiving shorter chemotherapy protocols, and with higher VO2peak at baseline. Moreover, we identified two significant interactions suggesting that disease stage and body mass index may differentially predict adherence to the three different exercise interventions. Patients who were overweight/obese or had more advanced disease stage adhered equally well to the standard dose aerobic exercise intervention, but struggled with the higher dose exercise interventions. The present study provides an empirical basis for improving exercise adherence in breast cancer patients on chemotherapy, including adherence to higher dose exercise interventions which may provide additional benefits for symptom management [] and even disease-free survival []. Additional research on the determinants of adherence to various exercise prescriptions during breast cancer chemotherapy is warranted.