The APAC study does not show different physiological functional impacts between three strategies of a home-based APA program during and/or after specific adjuvant treatment in patients with early-stage breast cancer. The between-group difference in VO2peak observed in the APAC study was not significant.
Although many APA studies involving breast cancer patients have been performed, few randomized controlled studies have been conducted during or after breast cancer chemotherapy. In addition, these studies showed that the performance of a home-based APA program increases VO2peak, but intensity, duration, and schedule programs vary among studies. During cancer-specific treatment, APA may increase treatment effectiveness to limit secondary effects, maintain physical fitness preventing muscle loss, fat gains, and fatigue, and improve QOL (32). Exercise post-treatment aims to accelerate recovery, improve physical fitness and QOL, and reduce fatigue. The aim of our study was to assess changes in VO2peak, an indicator of cardiorespiratory fitness, after an APA program started at different times in breast cancer patients.
In this trial, we compared the feasibility and benefits of a home-based PA program during or after specific cancer treatment to provide recommendations for patients undergoing breast cancer treatment. This AP program combined aerobic and resistance exercises, as proposed for the majority of trials for cancer patients (33). We did not compare the VO2 values with a control group without AP because it would not have been ethical to perform breast cancer adjuvant treatment without proposing an APA program, even if the modality is not precise. Previous reports have mostly assessed the impact of AP at the end of the AP program. In our study, the first objective was home-based exercise training impact on VO2max evaluated at 12 months after starting the AP program. In this trial, we measured cardiorespiratory fitness with VO2max using a cycle ergometer with breath-by-breath expired gas analysis, while many studies on home-based PA apply the 6-month walking test. Secondary objectives included exhaustive assessments on physical capacity, body composition, QOL, and anxiety and depression.
Breast cancer survivors have been reported as having VO2max values 22–25% lower compared to their age-matched healthy, sedentary non-cancer peers (11, 34). Low cardiorespiratory fitness is known to be inversely associated with breast cancer-related deaths, cardiovascular, and all-cause mortality (10, 35). In this trial, the significant increase in VO2 after APA was confirmed. However, at 12 months, APA did not increase the VO2max differently between the three groups A, B, and C. Group A maintained at T2 the improvement in VO2 obtained after 6 months of APA (as shown previously in SAPA trial), whereas Group B increased VO2 after their APA program despite a decrease in T1, and this increase recovered the value obtained in group A and C.
At T1, patients received chemotherapy and radiotherapy and comparison between groups A + C versus B showed the classical decrease in VO2 with chemotherapy alone and an increase when AP was performed concomitantly with chemotherapy. These changes were significantly different within each group but were not different between groups. These results support the findings of previous studies, but the VO2 improvement of 0.9 ± 2.7 mL min− 1 kg− 1 was lower than those obtained by Courneya et al. (36) (2.7 ± 2.6 mL min− 1 kg− 1) and in our previous SAPA protocol (2.26 ± 1.53 mL min− 1 kg− 1 in intention-to-treat analysis and 3.49 ± 1.64 mL min− 1 kg− 1 based on per-protocol analysis) (22). Typical curves of VO2peak evolution during the protocol were observed, and the lack of difference among the groups may be explained based on the following hypotheses. The number of patients included in the protocol was calculated based on a planned difference in VO2peak too high among the groups; in group C, the low adherence to APA from T0 to T1 may have been due to the high proportion of patients who were overweight or obese. The explications of the coach to patients highlighted the importance of PA and the aim of this protocol may explain why the majority of patients in group A maintained their adherence to PA after T1, contrary to published series (37, 38); the majority of patients in the three groups performed exercise at moderate levels based on the Polar monitor or questionnaires, which are commonly used for home-based exercise programs. These differences showed a heterogeneity of program performance and VO2 peak status was initially low in the majority of patients despite the average age being younger than normal in patients with breast cancer. Because we expressed the results as VO2peak means, we cannot discuss the within-group and between-group heterogeneity of results: 66% of patients in group A showed increased VO2 compared to 83% of group C.
The same variations were obtained in the 6-min walking tests than in VO2peak, supporting the concordance of these tests. A significant difference was observed at T1 between group A and C compared to group B, with a decrease in group B during chemotherapy performed without the AP program. A continued increase in walking meters was obtained in group C from T0 and T2, even if no significantly different values were present at T2 compared to group A and B.
Under any APA program performed by patients that was assessed with questionnaires, patients were considered to perform a moderate level of PA during the week. However, we found no associations between post-intervention changes in VO2max and changes in self-reported moderate to vigorous PA, revealing some limitations of these questionnaires. With a more accurate evaluation of the percentage of the program performed by patients, we found that the majority of patients performed 85% or more of the APA program, but it was difficult to measure the true expended calories because of difficulties using the Polar monitor. The APA program was performed in accordance with international PA recommendations for adults (39–41).
Cancer-related fatigue has been reported in up to 90% of people with cancer during adjuvant treatment with radiation therapy, chemotherapy, and endocrine therapy (42). Meta-analysis has shown that APA has a significant positive effect on fatigue (43–47) and QOL (48). In our study, fatigue evaluated based on MFI was stable without aggravation despite chemotherapy, except in group B, in which fatigue increased during chemotherapy with no difference between groups. A positive effect on QOL without deterioration was present in the three groups but was smaller than expected. A bias in evaluation in these questionnaires highlights the meaning of the personal self-evaluation, with changes in internal standards values and conceptualization of QOL, as reported previously (49). Only emotional state was considered at T1 to differ significantly when patients performed APA during specific treatments. All patients decreased their anxiety based on the HADS questionnaires, as described previously.
No change was observed in BMI and body composition based on absorptiometry. This stability was significant, as described previously (37), and may be explained by the absence of diet control. Muscle strength increased after APA, and a decrease was only observed in group B at T1 but reached the other groups at T2. This result was important because resistance training was not supervised and performed only once a week. The same increase was described in a study by Wanderson (50); two or three sessions were recommended in other previous reports (51) and the maintenance of muscular strength is known to have repercussions on QOL. In a study by Shilz et al. (53), 60% of breast cancer survivors suffered from significant decreases in muscle strength, thereby reducing QOL.
These results on VO2peak and muscular strength are encouraging to establish recommendations because they are known to facilitate PA behavior. It has been shown that exercise programs that improve or at least maintain physical fitness during breast cancer chemotherapy improve long-term exercise adherence (52); VO2peak can predict aerobic exercise behaviors and muscular fitness resistance. The moderate PA performed in these three groups may affect long-term exercise behavior since previous studies reported controversial results depending on the PA intensity with no impact of PA level (53) or intensity (54). A strength of our study is the exhaustive assessments with validated measures and addressing areas of physical performance, body composition, symptoms, and QOL.