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Effects of Aerobic and Resistance Exercise in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Multicenter Randomized Controlled Trial
Abstract
Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.
We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy–Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.
The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.
Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.
Adjuvant combination chemotherapy for early-stage breast cancer improves survival, but it may also cause unfavorable changes in quality of life (QOL),1 fatigue,2 physical functioning,3 and body composition.4 Few interventions have been shown to prevent these declines. Although exercise training has been considered, few studies have focused on breast cancer patients receiving chemotherapy, and the quality of the evidence is modest.5-7 In particular, study samples have been small and/or clinically heterogeneous (ie, mixed cancer sites on mixed treatment modalities), and no study has compared aerobic with resistance exercise. Moreover, few studies have examined body composition end points or lymphedema rates, and no study has documented chemotherapy completion rates. Consequently, the safety, efficacy, and optimal mode of exercise training in breast cancer patients receiving chemotherapy are still unknown.
Here, we report results from the Supervised Trial of Aerobic Versus Resistance Training (START), which examined the independent effects of aerobic and resistance exercise on QOL, fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rates, and lymphedema rates in breast cancer patients receiving adjuvant chemotherapy. We hypothesized that both aerobic exercise training (AET) and resistance exercise training (RET) would be superior to usual care (UC) for the patient-rated outcomes. For the objective outcomes, we hypothesized that AET would have beneficial effects on aerobic fitness and body fat levels, whereas RET would have beneficial effects for muscular strength and lean body mass. We did not expect either exercise intervention to cause lymphedema or interfere with chemotherapy completion rates.
Participants were recruited from the Cross Cancer Institute (Edmonton, Alberta, Canada), the Ottawa Hospital Integrated Cancer Program (Ottawa, Ontario, Canada), and the British Columbia Cancer Agency (Vancouver, British Columbia, Canada). The trial received ethical approval from all three centers and written informed consent from all participants. Eligibility criteria included English- or French-speaking nonpregnant women ≥ 18 years old with stage I to IIIA breast cancer who were beginning first-line adjuvant chemotherapy. Women were excluded if they had incomplete axillary surgery, transabdominal rectus abdominus muscle reconstructive surgery, uncontrolled hypertension, cardiac illness, psychiatric illness, or if they were otherwise not approved by their oncologist.
The study was a prospective, three-armed, randomized controlled trial. Eligible participants were identified by their treating oncologist before chemotherapy. Interested participants completed a questionnaire, physical fitness test, and dual x-ray absorptiometry scan (added after the first 23 participants were randomly assigned).
Participants were stratified by center and chemotherapy protocol (taxane based v non–taxane based) and randomly assigned to AET, RET, or UC in a 1:1:1 ratio using a computer-generated program. The allocation sequence was generated in Edmonton and concealed from the project directors at each site who assigned participants to groups.
Participants exercised for the duration of their chemotherapy, including delays, beginning 1 to 2 weeks after starting chemotherapy and ending 3 weeks after chemotherapy. Warm-up and cool-down periods were 5 minutes of light aerobic activity and stretching. The AET group was asked to exercise three times per week on a cycle ergometer, treadmill, or elliptical beginning at 60% of their maximal oxygen consumption, or VO2max, for weeks 1 to 6 and progressing to 70% during weeks 7 to 12 and 80% beyond week 12.8 Exercise duration began at 15 minutes for weeks 1 to 3 and increased by 5 minutes every 3 weeks until the duration reached 45 minutes at week 18. The RET group were asked to exercise three times per week performing two sets of eight to 12 repetitions of nine different exercises at 60% to 70% of their estimated one-repetition maximum.9 The exercises were leg extension, leg curl, leg press, calf raises, chest press, seated row, triceps extension, biceps curls, and modified curl-ups. Resistance was increased by 10% when participants completed more than 12 repetitions. The UC group was asked not to initiate an exercise program and was offered a 1-month exercise program after postintervention assessments.
Patient-rated outcomes were assessed at baseline (1 to 2 weeks after starting chemotherapy), midpoint (middle of chemotherapy), after the intervention (3 to 4 weeks after chemotherapy), and the 6-month follow-up (data not presented). Cancer-specific QOL and fatigue were assessed by the Functional Assessment of Cancer Therapy–Anemia scale.10 Psychosocial functioning was assessed by the Rosenberg Self-Esteem Scale,11 the Center for Epidemiological Studies Depression Scale,12 and the Spielberger State Anxiety Inventory.13
Objectively measured outcomes were assessed at baseline and after intervention. Aerobic fitness was evaluated using a maximal incremental exercise protocol on a treadmill.14 Expired gases were analyzed using a metabolic measurement cart (CPX-D; Medical Graphics, St Paul, MN). Peak oxygen consumption was determined by taking the highest values during a 15-second period. Muscular strength was assessed by an eight-repetition maximum on the horizontal bench press and leg extension.15 The maximum weight and number of repetitions were used to estimate the one-repetition maximum.15 Body weight to the nearest 0.1 kg and standing height to the nearest 0.5 cm were assessed without shoes using a balance beam scale (Health-o-Meter; Jarden Corporation, Rye, NY). A dual x-ray absorptiometry scan was obtained for the assessment of whole body fat and lean tissue using the Hologic QDR-4500 (Hologic, Bedford, MA) in Vancouver and the General Electric LUNAR EXPERT (GE, Piscataway, NJ) in Ottawa and Edmonton. Lymphedema was assessed using standard volumetric arm measurements based on water displacement.16 Chemotherapy completion rate was assessed as the average relative dose-intensity (RDI) for the originally planned regimen based on standard formulas.17,18
Demographic and behavioral data were collected by self-report, and medical data were abstracted from records. Exercise trainers monitored adherence and adverse events. Nonprotocol exercise was assessed by self-report.19
With 80 participants per group, our trial had 0.80 power to detect a difference in change scores of 7 points (standard deviation = 16) on the Functional Assessment of Cancer Therapy–Anemia scale10 with a loss-to-follow-up of 10%, a two-tailed α < .05, and no adjustment for multiple testing. Baseline comparisons were performed using univariate analysis of variance for continuous variables and χ2 analyses for categoric variables. Mixed-model analysis was used to model each outcome measure at three (or two) time points and compare the differences across groups in changes over time.20 Our primary analysis was unadjusted, but we also performed adjusted analyses controlling for baseline value of the outcome, age, marital status, employment status, disease stage, chemotherapy protocol, exercise status, and smoking status, using baseline propensity scores21 for being assigned to the RET and AET groups. We provide descriptive data and 95% CIs for all possible comparisons but provide significance tests (P values) only for hypothesized comparisons. For all analyses, we used the intent-to-treat principle. Available data for participants with missing data were included under the missing at random assumption of the mixed-model analysis.
Recruitment was from February 2003 to July 2005 (Fig 1). We recruited 242 (33%) of 736 eligible participants. The most common reasons for refusal were lack of interest (n = 131), too far to travel (n = 96), and too busy (n = 64). We obtained follow-up data on the patient-rated outcomes from 223 (92.1%) of 242 participants (Fig 1), which did not differ by group (P = .379). The most common reason for loss to follow-up was that the participant was unreachable after multiple attempts (n = 9).
The groups were balanced at baseline (Table 1). The median length of the exercise intervention was 17 weeks (95% CI, 9 to 24 weeks), and the mean length of treatment was 17 ± 4 weeks. The AET and RET groups attended 72.0% (2,685 of 3,750 sessions) and 68.2% (2,810 of 4,079 sessions) of their supervised exercise sessions, respectively (P = .411). The AET group met their prescribed duration and intensity 95.6% and 87.2% of the time, respectively. The RET group completed all nine exercises, two sets each, and eight to 12 repetitions each set 96.8%, 96.9%, and 94.5% of the time, respectively. Less than 15% of participants reported regular exercise outside of the trial, which did not differ by group (P > .2).
Table 2 presents the patient-rated outcomes. Self-esteem was superior in the AET (P = .015) and RET (P = .018) groups compared with UC. All other changes in patient-rated outcomes favored the exercise groups but did not reach statistical significance. Results were unchanged after adjustment for covariates (Table 2).
Table 3 lists the physical fitness end points. Peak oxygen consumption was superior in the AET group compared with the UC (P = .006) and RET (P = .014) groups. Lower body and upper body strength were superior in the RET compared with the UC (P < .001) and AET (P < .001) groups. Results were unchanged after adjustment for covariates (Table 3). Table 4 lists the body composition end points. Lean body mass was superior in the RET group compared with the UC group (P = .015). Adjusted analyses showed that the AET group was borderline superior to the UC group in percent body fat (adjusted P = .076). The percentage of participants who experienced a ≥ 200-mL increase in the difference between their affected and unaffected arm volumes from baseline to after intervention was 7.3% (six of 82 patients) in the UC group, 3.7% (three of 82 patients) in the RET group, and 9.0% (seven of 78 patients) in the AET group (P = .381).
RDI was 84.1% in the UC group compared with 89.8% in the RET group (mean difference = 5.7%; 95% CI, 0.4% to 11.0%; P = .033) and 87.4% in the AET group (mean difference = 3.3%; 95% CI, −2.5% to 9.2%; P = .266). The percentage of participants who received ≥ 85% of their planned RDI was 65.9% (54 of 82 patients) in the UC group compared with 78.0% (64 of 82 patients) in the RET group (mean difference = 12.1%; P = .082) and 74.4% (58 of 78 patients) in the AET group (mean difference = 8.5%; P = .241).
Exercise adherence in both groups was positively associated with a higher RDI (r = 0.17; P = .035). AET adherence was associated with greater improvements in aerobic fitness (r = 0.24; P = .036). RET adherence was associated with greater improvements in lower body strength (r = 0.61; P < .001), upper body strength (r = 0.53; P < .001), and lean body mass (r = 0.25; P = .037). For the AET versus UC comparison, improvements in aerobic fitness were associated with improvements in QOL (r = 0.26; P = .001), fatigue (r = 0.25; P = .002), depression (r = −0.24; P = .003), and anxiety (r = −0.18; P = .025). For the RET versus UC comparison, improvements in lean body mass were associated with improvements in QOL (r = 0.19; P = .022), self-esteem (r = 0.19; P = .022), depression (r = −0.19; P = .019), and percentage of participants completing ≥ 85% of their planned RDI (r = 0.15; P = .074). Improvement in lower body strength was associated with improvement in QOL (r = 0.15; P = .057).
Two participants experienced an adverse event related to exercise after baseline maximal treadmill testing. One participant became lightheaded, hypotensive, and moderately nauseous. A second participant experienced dizziness, weakness, and mild diarrhea. Both participants recovered quickly.
Contrary to our hypotheses, neither AET nor RET significantly improved cancer-specific QOL, fatigue, depression, or anxiety, although the trends favored the exercise groups. Consistent with our hypotheses, AET significantly improved self-esteem, preserved aerobic fitness, and maintained body fat levels, whereas RET significantly improved self-esteem, muscular strength, and lean body mass. Unexpectedly, RET significantly improved chemotherapy completion rate. Neither intervention caused lymphedema or significant adverse events.
Few published studies are available for direct comparisons. A recent meta-analysis5 of 14 exercise randomized controlled trials in breast cancer patients/survivors revealed that published trials have either focused on the postadjuvant therapy setting or combined breast cancer patients on various adjuvant therapies (eg, chemotherapy, radiation therapy, hormonal therapy). Trials in the postadjuvant setting have shown that both aerobic22 and resistance23 exercise can improve cancer-specific QOL. Only one trial in the adjuvant therapy setting reported data separately for patients on chemotherapy, although it was not powered for such a subanalysis.24 In that trial, there were no effects of 26 weeks of lower intensity supervised or self-directed aerobic exercise on QOL.
The failure of our exercise interventions to significantly improve cancer-specific QOL may be, in part, a result of the wide variability in QOL change scores we found during chemotherapy (standard deviation = 25). Many uncontrollable factors influence QOL during chemotherapy, and a global measure of cancer-specific QOL may be too broad to detect the likely narrower effects of exercise training. A more appropriate and realistic primary end point in exercise trials may be the physical functioning component of QOL.25 It is also possible that the effects of our exercise interventions were partly diluted by inadequate adherence and/or an insufficient volume/intensity of exercise. However, it is unclear whether better adherence or a greater volume/intensity of exercise can be achieved in this clinical setting. Our adherence rate is within the range commonly reported in exercise RCTs in breast cancer patients receiving adjuvant therapy5 and older adults without cancer.26 Nevertheless, there is clearly still room for improvement, and we plan a full report of the predictors of exercise adherence in our trial to facilitate this improvement.
Changes in fatigue, depression, and anxiety also favored the exercise groups but did not achieve statistical significance. These findings are consistent with three recent meta-analyses5-7 that have reported modest effects on these outcomes and noted that the stronger and more consistent effects appear in the postadjuvant setting. Conversely, both exercise interventions improved self-esteem, which is an important outcome for breast cancer patients going through difficult treatments.27 There is no identified important difference for our scale, but the standardized effect size was small to moderate (d = 0.30). Previous exercise trials have not examined self-esteem during chemotherapy but have noted improvements in the postadjuvant therapy setting with aerobic exercise.22
Although patient-rated outcomes primarily showed trends in favor of the exercise groups, the objectively measured outcomes were reliably changed. AET blunted a decline in maximal oxygen consumption in the UC group of approximately 2.0 mL/mg/kg, or 8%. Training studies in other populations show slightly larger improvements of 10% to 30%,8 although few have conducted intent-to-treat analyses. Segal et al24 reported no effects of a lower intensity exercise program on aerobic fitness in the subanalysis of breast cancer patients receiving chemotherapy. Our trial demonstrates that a higher intensity exercise program can preserve aerobic fitness in breast cancer patients even in the face of a downward trajectory in aerobic fitness, possibly caused by chemotherapy effects such as anemia, tachycardia, dehydration, and cardiac dysfunction.3,28 Preserving aerobic fitness in breast cancer patients receiving chemotherapy may be beneficial. In our trial, improved aerobic fitness was associated with improved QOL, fatigue, depression, and anxiety, suggesting that greater increases in aerobic fitness may have resulted in better patient-rated outcomes. Aerobic fitness is also an established predictor of disease and mortality.29
RET increased muscular strength by 25% to 35%, which is consistent with research in other populations.9 To our knowledge, our study is the first to test the effects of an isolated resistance training program in breast cancer patients receiving chemotherapy. Schmitz et al30 demonstrated improvements in muscular strength of 30% to 50% in the postadjuvant setting. The clinical implications of improved muscular strength for breast cancer patients are unknown, but we did observe a modest correlation between increased muscular strength and improved QOL, as did Ohira et al.23 In other populations, muscular strength is associated with improved physical functioning, reduced mobility limitations and lower risk of falling,23,31,32 and lower mortality.33
Neither exercise intervention prevented weight gain, but each altered body composition as hypothesized. AET prevented fat gain, and RET added lean body mass. Weight gain after a breast cancer diagnosis has been associated with earlier recurrence and shorter survival,34 with most explanations focusing on adiposity rather than body weight per se.35 Moreover, in our trial, improvements in body composition were associated with improvements in QOL, self-esteem, and depression, suggesting that body composition may have implications for psychosocial functioning in addition to clinical outcomes. Schmitz et al30 reported similar improvements in body composition with resistance training in the postadjuvant setting but also found no change in body weight. Associations between improved lean body mass and QOL were also reported.23 A systematic review of 14 exercise intervention studies in breast cancer patients/survivors concluded that there were few changes in body weight but some improvements in body composition.36
Unexpectedly, RET improved chemotherapy completion rate. Clinical trials support the importance of sustaining full dose-intensity in adjuvant chemotherapy for early-stage breast cancer with evidence of a threshold effect of approximately 85%.37-39 The clinical implications of an RDI difference of 5.7% found in our study are unclear, but most studies have noted a steep association between RDI and clinical outcomes to the 85% threshold.37-39 The explanation for the difference in chemotherapy completion rate is unclear. The groups were balanced on chemotherapy regimens, and the UC group actually received more granulocyte colony-stimulating factor than the RET group (P = .013) after excluding prophylactic granulocyte colony-stimulating factor use. Acute exercise is known to cause demargination of neutrophils and a temporary increase of 25% to 100% in peripheral-blood neutrophil count lasting up to 6 hours,40 which, theoretically, could alter chemotherapy delivery decisions. Given the exploratory nature of this finding, it should be replicated before it is considered reliable.
Neither AET nor RET caused arm swelling or other adverse events. To our knowledge, our trial is the first to report lymphedema data for the adjuvant chemotherapy time period, but it is consistent with previous smaller studies in the postadjuvant therapy setting.16,41-43 Few exercise trials in breast cancer patients have reported adverse events, but our trial suggests that adverse events may be minimal.
Our trial's strengths include the direct comparison of aerobic and resistance exercise, the largest sample size to date, the well-defined population, the multicenter recruitment, the supervised exercise, a comprehensive assessment of important end points with validated measures, intent-to-treat analysis, and limited loss to follow-up. Limitations include the 70% adherence rate, the 33% recruitment rate, and the well-educated, racially homogenous sample. Moreover, given the 22 group comparisons we made at the α = .05 level, we would expect one false discovery by chance if all of these comparisons were actually null.
In summary, our trial demonstrates important improvements in self-esteem, physical fitness, body composition, and possibly chemotherapy completion rate from exercise training in breast cancer patients receiving chemotherapy. Our findings may help explain a recent observational study reporting a positive association between physical activity and survival in breast cancer survivors.44 Cancer care professionals should consider recommending either AET or RET to breast cancer patients receiving chemotherapy. A combined intervention may be optimal, but research is needed to confirm this assumption, especially given the challenges of exercise adherence in this clinical setting.
The author(s) indicated no potential conflicts of interest.
Conception and design: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Donald C. McKenzie
Financial support: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Donald C. McKenzie
Administrative support: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Yutaka Yasui, Donald C. McKenzie
Provision of study materials or patients: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Donald C. McKenzie
Collection and assembly of data: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Donald C. McKenzie
Data analysis and interpretation: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Yutaka Yasui, Donald C. McKenzie
Manuscript writing: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Yutaka Yasui, Donald C. McKenzie
Final approval of manuscript: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Yutaka Yasui, Donald C. McKenzie
Fig 1. Flow of participants through the trial. PRO, patient-rated outcomes.
|
| Variable | Overall (n = 242) | Usual Care (n = 82) | RET (n = 82) | AET (n = 78) | P | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of Patients | % | No. of Patients | % | No. of Patients | % | No. of Patients | % | ||||||
| Demographic profile | |||||||||||||
| Age, years | .946 | ||||||||||||
| Mean | 49.2 | 49.0 | 49.5 | 49.0 | |||||||||
| Range | 25-78 | 26-78 | 25-76 | 30-75 | |||||||||
| Married | 154 | 63.6 | 51 | 62.2 | 47 | 57.3 | 56 | 71.8 | .155 | ||||
| Completed university | 155 | 64.0 | 53 | 64.6 | 51 | 62.2 | 51 | 65.4 | .907 | ||||
| Income > $80,000/yr* | 103 | 45.0 | 34 | 42.5 | 41 | 53.9 | 28 | 38.4 | .138 | ||||
| Full-time employed | 72 | 29.8 | 23 | 28.0 | 29 | 35.4 | 20 | 25.6 | .371 | ||||
| Medical profile | |||||||||||||
| Weight, kg | .282 | ||||||||||||
| Mean | 70.6 | 72.6 | 69.7 | 69.4 | |||||||||
| SD | 14.3 | 15.2 | 14.4 | 13.3 | |||||||||
| BMI, kg/m2 | .518 | ||||||||||||
| Mean | 26.6 | 27.1 | 26.1 | 26.7 | |||||||||
| SD | 5.5 | 5.4 | 5.5 | 5.6 | |||||||||
| Obese | 50 | 20.7 | 19 | 23.2 | 14 | 17.1 | 17 | 21.8 | .600 | ||||
| Hypertension | 17 | 7.0 | 4 | 4.9 | 8 | 9.8 | 5 | 6.4 | .458 | ||||
| Postmenopausal | 89 | 36.8 | 27 | 32.9 | 35 | 42.7 | 27 | 34.6 | .558 | ||||
| Disease stage | .344 | ||||||||||||
| I (T1N0) | 60 | 24.8 | 20 | 24.4 | 22 | 26.8 | 18 | 23.1 | |||||
| IIa (T1N1, T2N0) | 99 | 40.9 | 30 | 36.6 | 36 | 43.9 | 33 | 42.3 | |||||
| IIb (T2N1, T3N0) | 48 | 19.8 | 22 | 26.8 | 9 | 11.0 | 17 | 21.8 | |||||
| IIIa (T1N2, T2N2, T3N1-2) | 35 | 14.5 | 10 | 12.2 | 15 | 18.3 | 10 | 12.8 | |||||
| Surgical protocol | .857 | ||||||||||||
| Breast conservation | 143 | 59.1 | 49 | 59.8 | 50 | 61.0 | 44 | 56.4 | |||||
| Chemotherapy protocol | .749 | ||||||||||||
| Nontaxane | 167 | 69.0 | 54 | 65.9 | 58 | 70.7 | 55 | 70.5 | |||||
| FE100C | 74 | 30.6 | 23 | 28.0 | 29 | 35.4 | 22 | 28.2 | |||||
| AC | 64 | 26.4 | 20 | 24.4 | 23 | 28.0 | 21 | 26.9 | |||||
| CE120F | 16 | 6.6 | 8 | 9.8 | 5 | 6.1 | 3 | 3.8 | |||||
| Other | 13 | 5.4 | 3 | 3.7 | 1 | 1.2 | 9 | 11.5 | |||||
| Taxane | 75 | 31.0 | 28 | 34.1 | 24 | 29.3 | 23 | 29.5 | |||||
| TAC | 34 | 14.0 | 10 | 12.2 | 12 | 14.6 | 12 | 15.4 | |||||
| AC-Taxane | 33 | 13.6 | 14 | 17.1 | 10 | 12.2 | 9 | 11.5 | |||||
| Other | 8 | 3.3 | 4 | 4.9 | 2 | 2.4 | 2 | 2.6 | |||||
| Behavioral profile | |||||||||||||
| Current exerciser | 64 | 26.4 | 27 | 32.9 | 22 | 26.8 | 15 | 19.2 | .145 | ||||
| Current weight trainer | 19 | 7.9 | 9 | 11.3 | 6 | 7.3 | 4 | 5.1 | .351 | ||||
| Current smoker | 20 | 8.3 | 5 | 6.1 | 9 | 11.0 | 6 | 7.7 | .513 | ||||
| Current drinker | 15 | 6.2 | 5 | 6.1 | 4 | 4.9 | 6 | 7.7 | .761 | ||||
Abbreviations: RET, resistance exercise training; AET, aerobic exercise training; SD, standard deviation; BMI, body mass index; FE100C, fluorouracil, epirubicin, cyclophosphamide; CE120F, cyclophosphamide, epirubicin, fluorouracil; AC, doxorubicin, cyclophosphamide; AC-Taxane, paclitaxel or docetaxel after AC; TAC, docetaxel, doxorubicin, cyclophosphamide.
*N = 229.
|
| Outcome | Baseline | Midpoint | Post-Test | Mean Change | Unadjusted Group Difference in Mean Change | Adjusted Group Difference in Mean Change | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | SD | Mean | 95% CI | Mean | 95% CI | P | Mean | 95% CI | P | |||||||||
| FACT-An | ||||||||||||||||||||||
| UC | 135.3 | 28.1 | 131.1 | 29.5 | 139.9 | 28.2 | 1.0 | −4.2 to 6.3 | 4.7* | −2.7 to 12.1 | .216 | 4.0* | −3.4 to 11.5 | .286 | ||||||||
| RET | 132.2 | 23.5 | 132.6 | 28.4 | 140.9 | 24.8 | 5.9 | 0.6 to 11.2 | 3.7† | −3.8 to 11.1 | .338 | 3.6† | −3.9 to 11.2 | .345 | ||||||||
| AET | 135.7 | 29.0 | 135.5 | 27.2 | 144.7 | 25.2 | 4.8 | −0.6 to 10.1 | 1.0‡ | −6.4 to 8.5 | 0.4‡ | −7.1 to 8.0 | ||||||||||
| Self-esteem | ||||||||||||||||||||||
| UC | 34.1 | 4.6 | 32.9 | 5.1 | 33.2 | 5.5 | −1.0 | −1.8 to −0.3 | 1.3* | 0.2 to 2.3 | .018 | 1.2* | 0.2 to 2.3 | .025 | ||||||||
| RET | 34.1 | 4.2 | 33.8 | 4.8 | 34.7 | 4.2 | 0.3 | −0.5 to 1.0 | 1.3† | 0.3 to 2.4 | .015 | 1.2† | 0.1 to 2.3 | .026 | ||||||||
| AET | 34.0 | 5.1 | 34.1 | 5.0 | 34.5 | 5.1 | 0.3 | −0.5 to 1.1 | 0.0‡ | −1.1 to 1.0 | 0.0‡ | −1.1 to 1.1 | ||||||||||
| Fatigue | ||||||||||||||||||||||
| UC | 34.6 | 11.1 | 32.3 | 12.3 | 34.9 | 12.5 | −0.7 | −3.2 to 1.8 | 1.5* | −2.0 to 5.0 | .393 | 1.7* | −1.8 to 5.2 | .338 | ||||||||
| RET | 34.3 | 10.1 | 33.1 | 11.3 | 36.3 | 9.4 | 0.9 | −1.6 to 3.3 | 1.0† | −2.5 to 4.5 | .561 | 1.5† | −2.1 to 5.0 | .415 | ||||||||
| AET | 35.3 | 12.1 | 34.0 | 11.5 | 36.8 | 10.4 | 0.4 | −2.1 to 2.9 | 0.5‡ | −3.0 to 4.0 | 0.2‡ | −3.3 to 3.8 | ||||||||||
| Anxiety | ||||||||||||||||||||||
| UC | 42.0 | 13.7 | 39.0 | 11.9 | 37.4 | 12.0 | −4.2 | −6.5 to −1.9 | −1.5* | 1.8 to −4.8 | .372 | −1.8* | 1.5 to −5.1 | .278 | ||||||||
| RET | 42.0 | 12.0 | 37.0 | 12.0 | 36.4 | 12.7 | −5.7 | −8.0 to −3.4 | −1.7† | 1.6 to −5.0 | .317 | −2.1† | 1.2 to −5.5 | .209 | ||||||||
| AET | 40.9 | 13.3 | 35.3 | 11.9 | 35.0 | 11.7 | −5.9 | −8.3 to −3.5 | 0.2‡ | 3.5 to −3.1 | 0.3‡ | 3.1 to −3.7 | ||||||||||
| Depression | ||||||||||||||||||||||
| UC | 13.9 | 9.7 | 13.7 | 10.2 | 10.8 | 9.4 | −1.9 | −3.8 to 0.1 | −0.4* | 2.4 to −3.2 | .774 | −0.6* | 2.2 to −3.4 | .679 | ||||||||
| RET | 13.8 | 10.1 | 12.6 | 9.4 | 10.6 | 9.5 | −2.3 | −4.3 to −0.3 | −0.3† | 2.5 to −3.1 | .841 | −0.8† | 2.0 to −3.6 | .571 | ||||||||
| AET | 12.8 | 9.8 | 12.2 | 9.8 | 9.7 | 9.3 | −2.2 | −4.2 to −0.2 | −0.1‡ | 2.7 to −2.9 | 0.2‡ | 3.1 to −2.6 | ||||||||||
NOTE. Mean (SD) at midpoint and post-test are based on available data. Mean change is based on combined post-test/midpoint scores minus baseline score but may not precisely reflect this difference given that mean change is estimated based on mixed-model analysis. Adjusted group difference in mean change was adjusted for baseline value of the outcome, age, marital status, employment status, disease stage, chemotherapy protocol, current exercise status, and smoking status. P values presented only for hypothesized comparisons.
Abbreviations: SD, standard deviation; FACT-An, Functional Assessment of Cancer Therapy–Anemia; UC, usual care; RET, resistance exercise training; AET, aerobic exercise training.
*RET v UC.
†AET v UC.
‡RET v AET.
|
| Measure | Baseline | Post-Test | Mean Change | Unadjusted Group Differences in Mean Change | Adjusted Group Differences in Mean Change | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | 95% CI | Mean | 95% CI | P | Mean | 95% CI | P | ||||||||
| VO2peak, mL/kg/min | |||||||||||||||||||
| UC | 24.8 | 6.2 | 23.5 | 5.4 | −1.6 | −2.6 to −0.7 | 1.8* | 0.5 to 3.2 | .006 | 2.0* | 0.6 to 3.3 | .004 | |||||||
| RET | 25.5 | 6.1 | 24.2 | 6.1 | −1.4 | −2.4 to −0.5 | 1.6† | 0.3 to 2.9 | .014 | 1.4† | 0.1 to 2.7 | .031 | |||||||
| AET | 25.2 | 7.2 | 25.7 | 7.4 | 0.2 | −0.7 to 1.1 | 0.2‡ | −1.1 to 1.5 | 0.5‡ | −0.8 to 1.8 | |||||||||
| VO2peak, L/min | |||||||||||||||||||
| UC | 1.76 | 0.40 | 1.68 | 0.36 | −0.10 | −0.16 to −0.03 | 0.13* | 0.04 to 0.22 | .004 | 0.12* | 0.03 to 0.21 | .010 | |||||||
| RET | 1.73 | 0.35 | 1.67 | 0.36 | −0.06 | −0.12 to −0.00 | 0.09† | 0.01 to 0.18 | .035 | 0.08† | −0.01 to 0.17 | .077 | |||||||
| AET | 1.72 | 0.43 | 1.77 | 0.48 | 0.03 | −0.03 to 0.09 | 0.03‡ | −0.05 to 0.12 | 0.04‡ | −0.05 to 0.12 | |||||||||
| 1RM leg, kg | |||||||||||||||||||
| UC | 25.6 | 12.6 | 27.1 | 14.1 | 1.4 | −0.5 to 3.3 | 6.7‡ | 4.0 to 9.3 | .001 | 6.8‡ | 4.2 to 9.5 | .001 | |||||||
| RET | 24.4 | 11.2 | 32.8 | 12.6 | 8.2 | 6.4 to 10.1 | 4.9§ | 2.3 to 7.6 | .001 | 5.2§ | 2.5 to 7.9 | .001 | |||||||
| AET | 24.8 | 12.5 | 28.2 | 14.2 | 3.3 | 1.3 to 5.2 | 1.7* | −1.0 to 4.4 | 1.6* | −1.1 to 4.3 | |||||||||
| 1RM chest, kg | |||||||||||||||||||
| UC | 22.8 | 8.9 | 24.6 | 7.8 | 1.5 | −0.4 to 3.4 | 7.4‡ | 5.2 to 9.6 | .001 | 7.7‡ | 5.5 to 9.9 | .001 | |||||||
| RET | 23.2 | 7.2 | 31.9 | 10.8 | 8.8 | 7.2 to 10.3 | 6.1§ | 3.9 to 8.4 | .001 | 6.8§ | 4.5 to 9.0 | .001 | |||||||
| AET | 22.1 | 7.5 | 24.7 | 7.5 | 2.6 | 1.0 to 4.3 | 1.3* | −1.0 to 3.6 | 1.0* | −1.3 to 3.2 | |||||||||
NOTE. Mean (SD) at post-test is based on available data. Mean change is based on post-test score minus baseline score but may not precisely reflect this difference given that mean change is estimated based on mixed-model analysis. Adjusted group difference in mean change was adjusted for baseline value of the outcome, age, marital status, employment status, disease stage, chemotherapy protocol, current exercise status, and smoking status. P values presented only for hypothesized comparisons.
Abbreviations: SD, standard deviation; VO2peak, peak volume of oxygen consumed; UC, usual care; RET, resistance exercise training; AET, aerobic exercise training; RM, repetition maximum.
*AET v UC.
†AET v RET.
‡RET v UC.
§RET v AET.
|
| Measure | Baseline | Post-Test | Mean Change | Unadjusted Group Differences in Mean Change | Adjusted Group Differences in Mean Change | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | 95% CI | Mean | 95% CI | P | Mean | 95% CI | P | ||||||||
| Body weight, kg | |||||||||||||||||||
| UC | 72.6 | 15.2 | 73.4 | 15.7 | 1.2 | 0.4 to 2.0 | −0.2* | 0.9 to −1.3 | .737 | −0.2* | 0.9 to −1.4 | .698 | |||||||
| RET | 69.7 | 14.4 | 71.1 | 15.4 | 1.6 | 0.8 to 2.4 | 0.4† | 1.6 to −0.7 | 0.5† | 1.6 to −0.6 | |||||||||
| AET | 69.4 | 13.3 | 70.3 | 13.8 | 1.0 | 0.2 to 1.8 | −0.6‡ | 0.5 to −1.8 | −0.7‡ | 0.4 to −1.9 | |||||||||
| Body fat, % | |||||||||||||||||||
| UC | 38.8 | 9.1 | 39.8 | 8.8 | 1.0 | 0.3 to 1.7 | −0.8* | 0.2 to −1.8 | .137 | −0.9* | 0.1 to −1.9 | .076 | |||||||
| RET | 37.2 | 9.0 | 37.2 | 9.0 | 0.3 | −0.4 to 1.1 | −0.6† | 0.4 to −1.6 | −0.9† | 0.1 to −1.9 | |||||||||
| AET | 37.8 | 8.9 | 37.9 | 8.9 | 0.2 | −0.5 to 0.9 | −0.2‡ | 0.9 to −1.2 | −0.0† | 1.0 to −1.0 | |||||||||
| Fat mass, kg | |||||||||||||||||||
| UC | 28.3 | 12.0 | 29.5 | 12.0 | 1.0 | 0.4 to 1.7 | −0.5* | 0.4 to −1.5 | .261 | −0.7* | 0.3 to −1.6 | .170 | |||||||
| RET | 26.2 | 11.7 | 26.9 | 12.0 | 0.9 | 0.3 to 1.6 | −0.1† | 0.8 to −1.1 | −0.2 | 0.8 to −1.2 | |||||||||
| AET | 26.6 | 11.5 | 27.1 | 11.3 | 0.5 | −0.2 to 1.2 | −0.4‡ | 0.5 to −1.4 | −0.5‡ | 0.5 to −1.5 | |||||||||
| Lean mass, kg | |||||||||||||||||||
| UC | 40.8 | 5.3 | 40.9 | 5.6 | 0.2 | −0.3 to 0.6 | 0.8† | 0.2 to 1.5 | .015 | 1.0† | 0.3 to 1.6 | .004 | |||||||
| RET | 40.3 | 4.6 | 41.3 | 4.9 | 1.0 | 0.5 to 1.5 | 0.4* | −0.3 to 1.0 | 0.3* | −0.3 to 1.0 | |||||||||
| AET | 40.3 | 4.8 | 40.9 | 5.1 | 0.5 | 0.1 to 1.0 | 0.4§ | −0.2 to 1.1 | 0.6§ | −0.1 to 1.3 | |||||||||
| Arm difference, mL | |||||||||||||||||||
| UC | 21 | 134 | 11 | 153 | −4 | −35 to 26 | 0.0† | −43 to 42 | −5† | −46 to 35 | |||||||||
| RET | 8 | 129 | 10 | 118 | −5 | −35 to 25 | 14* | −29 to 57 | −9* | −50 to 32 | |||||||||
| AET | −18 | 101 | −7 | 152 | 10 | −21 to 40 | −14§ | −57 to 28 | −4§ | −45 to 38 | |||||||||
NOTE. Mean (SD) at post-test is based on available data. Mean change is based on post-test score minus baseline score but may not precisely reflect this difference given that mean change is estimated based on mixed-model analysis. Adjusted group difference in mean change was adjusted for baseline value of the outcome, age, marital status, employment status, disease stage, chemotherapy protocol, current exercise status, and smoking status. P values presented only for hypothesized comparisons.
Abbreviations: SD, standard deviation; UC, usual care; RET, resistance exercise training; AET, aerobic exercise training.
*AET v UC.
†RET v UC.
‡AET v RET.
§RET v AET.
published online ahead of print at www.jco.org on September 4, 2007.
Supported by a grant from the Canadian Breast Cancer Research Alliance; the Canada Research Chairs Program (K.S.C. and Y.Y.); a Research Team Grant from the National Cancer Institute of Canada (NCIC) with funds from the Canadian Cancer Society (CCS) and the NCIC/CCS Sociobehavioral Cancer Research Network (K.S.C., R.J.S., D.C.M., J.R.M., C.M.F.); a New Investigator Award from the Heart and Stroke Foundation of Canada (R.D.R.); a New Investigator Award from the Canadian Institutes of Health Research and a Health Scholar Award from the Alberta Heritage Foundation for Medical Research (C.M.F.); and by a Canada Graduate Scholarship from the Canadian Institutes of Health Research and an Incentive Award from the Alberta Heritage Foundation for Medical Research (J.K.V.).
The Canadian Breast Cancer Research Alliance had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
We gratefully acknowledge Lisa Workman, MA, Neil Eves, PhD, John McGavock, PhD, Kristin Campbell, PhD, Margaret McNeely, BScPT, MSc, Diana Jespersen, BA, Chris Scott, BSc, Ben Wilson, BSc, Christopher Sellar, MS, and Diane Cook, BA, for their assistance in recruitment, exercise supervision, testing, data management, and manuscript preparation.
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