Abstract
Introduction: Breast cancer patients (BCP) experience considerable side effects during and after treatment. Several studies have shown positive effects of exercise on therapy-related side-effects such as loss of muscle strength, loss of bone mineral density, lymphedema, and several elements of quality of life (QoL). Resistance exercise has proven effective and beneficial for BCP; however, optimal individual training parameters remain to be determined. Methods: The aim of our study was to implement an adaptive, progressive, supervised resistance protocol for BCPs during chemotherapy, improving muscle strength, physical condition, and overall QoL while reducing therapy-induced side-effects. Forty patients receiving adjuvant chemotherapy were included 6–12 weeks post-OP. Twenty patients underwent high intensity resistance-training twice a week for 12 weeks, and the control group received usual care. Results: Strength parameters improved significantly in the intervention group and in different scales of QoL. We documented a cyclic performance level dependent on the number of days after treatment. Conclusion: Adaptive resistance training with simple training control mechanisms proved to be effective regarding optimal intensity in each training session and needs to be implemented in further studies in order to guarantee adequate loads in accordance to the training protocols.
Introduction
Breast cancer (BC) is the most common cancer in women worldwide [1]. Despite the increasing incidence rate, advanced medical treatment has improved the chance for cure. Five-year survival rates increased to around 90% in 2017 [2], leading to more patients living with cancer for a longer time. However, breast cancer patients (BCPs) experience considerable side effects during and after treatment. Side-effects and symptoms include, amongst others, reduced strength, fatigue, loss of bone mineral density, reduced range of motion (especially in the arms and shoulders), lymphedemas, polyneuropathy, emesis and negative effects on quality of life (QoL) [3‒5]. Adding to the latter are depression, anxiety and other psychological factors as well as a negative influence on exercise [6]. Treatment may lead to chronification of side-effects and comorbidities such as metabolic syndrome [7]. Several studies have shown positive effects of exercise on therapy-related side-effects, such as loss of muscle strength [8, 9], loss of bone mineral density [10], lymphedemas [11], and several elements of QoL [12, 13].
Exercise has been proven to be a potent approach to benefit BCPs in many ways, improving their physical condition and reducing treatment-associated impairments [14]. Mok et al. [15] conclude in their systematic review and meta-analysis that resistance interventions elicited higher benefits regarding mental wellbeing and physical fitness during adjuvant therapy. Progressive and high intensity resistance training for BCP is considered safe [9, 11, 16]. Furmaniak et al. [17] listed in their Cochrane review 13 studies on BCP during adjuvant treatment that utilized different resistance training regimes. Eight of these studies evaluated strength as an outcome but only Van Waart et al. [18] conducted high intensity training. Two of the aforementioned studies had multiple arms with resistance exercise as one of the interventions [8, 10]. Cornette et al. [19] performed supervised resistance training followed by home-based aerobic resistance training. Most studies emphasize the stabilization of muscular strength during chemotherapy through resistance training, and improvements in strength parameters are uncommon.
Resistance exercise has proven to be effective, safe, and beneficial for BCP; however, optimal individual training parameters (dose, timing, type, and intensity) remain to be determined [9, 20, 21]. Resistance training prescriptions for cancer patients should be individualized, considering factors such as age, menopausal status, obesity, past exercise experience, initial fitness level, and treatment protocol. Identifying the right frequency, intensity, periodization, and sequencing is a necessary step toward individualized exercise guidelines for BCP [22]. Varying levels of strength under the impact of the aforementioned factors make adaptive resistance training protocols and thus effective training control a necessary part of exercise science as well as of clinical practice and home-based programs in BCP.
Improved treatment and survival highlight the importance of QoL in the long-term treatment of BC patients. We could not find a study that documented resistance/weight in training sessions and a form of training control. The aim of our study was to implement an adaptive, progressive, supervised resistance protocol for BCP during chemotherapy, with the aim of improving muscle strength, physical condition, and overall QoL while reducing therapy-induced side-effects.
Methods
Study Design
The Valesco Study was carried out as a prospective, controlled, non-randomized preference study to evaluate a 12-week resistance training in patients with stage I-III BC during adjuvant chemotherapy. Forty patients receiving adjuvant chemotherapy were included 6–12 weeks post-surgery. 20 patients underwent one-on-one resistance training twice weekly for 12 weeks. The remaining 20 patients formed the control group and received usual care. End points were measured 5–10 days after receiving the second dose of chemotherapy (baseline T0), after 6 weeks (T1), and post-intervention, after 12 weeks (T2), again 5–10 days after treatment.
The primary endpoint was change in muscular strength. The secondary endpoint was QoL. The inclusion and exclusion criteria are presented in Table 1.
Inclusion criteria . | Exclusion criteria . |
---|---|
Female patients with BC (stages I-III), receiving adjuvant chemotherapy or combined chemo-/radiotherapy | Severe cardiac or cardiovascular disease |
Operation within 6–12 weeks before inclusion | Severe chronical diseases prohibiting physical activity |
ECOG performance status <2 | Intense physical activity of more than 2 h per week apart from intervention |
At least 18 years of age | Metastases |
Written informed consent | Substance abuse (drugs or alcohol) |
Ability to understand study protocol and questionnaires | No legal competence |
Inclusion criteria . | Exclusion criteria . |
---|---|
Female patients with BC (stages I-III), receiving adjuvant chemotherapy or combined chemo-/radiotherapy | Severe cardiac or cardiovascular disease |
Operation within 6–12 weeks before inclusion | Severe chronical diseases prohibiting physical activity |
ECOG performance status <2 | Intense physical activity of more than 2 h per week apart from intervention |
At least 18 years of age | Metastases |
Written informed consent | Substance abuse (drugs or alcohol) |
Ability to understand study protocol and questionnaires | No legal competence |
Recruitment
Recruitment was performed at the breast center outpatient clinic of the University Hospital Cologne between November 2010 and January 2013. Eligible patients were informed in detail by the study physicians and contacted by the study coordinators after written consent was obtained. Patients underwent baseline assessment 5–10 days after receiving the second dose of chemotherapy. Baseline assessment was performed at the German Sports University Cologne with strength testing outsourced to ProPhysio Cologne. All tests for each patient were performed on the same day.
Intervention
The patients in the intervention groups were administered for approximately 45–60 min twice weekly over a period of 12 weeks under the supervision of experienced therapists in a special training facility for physiotherapy. All training sessions were conducted in a one-on-one setting with the therapist concentrating on 1 patient only. Intervention started 2–4 days after baseline measurements. Each training session consisted of a 10-min warm-up on a stationary bike or treadmill and seven resistance exercises in varying order: leg press, seated back-extension, seated pulldowns, seated dips, seated leg curls, parallel cable-row with external rotation (seated or standing), and internal shoulder rotation (seated). There was a warm-up set of 10–15 repetitions on each machine followed by two high-intensity sets of 70–80% h1RM. The warm-up set was used to determine the adequate weight for the following two sets. The following sets consisted of 8–12 repetitions until muscular exertion. The three sets had to be finished on each machine with 1 min of rest between sets. Rest between different exercises was partially longer. The subjective rate of physical exhaustion was recorded after each exercise using the modified RPE-Scale. Resistance was modified for each session to closely match the target-intensity. Physical status, adverse events, adherence were recorded for each session.
Outcome Measures
The primary end point was improvement of muscle strength from baseline to T2. Muscle strength parameters were assessed by using an isokinetic dynamometer (Biodex System 2). Knee-flexion and -extension, elbow-flexion, and -extension as well as shoulder-rotation were measured in two isometric positions and one dynamic setting. Isometric angles for the knee were 36° and 63° while the range of motion for the isokinetic measurement was set from 0° to 80° with the dynamometer-speed set to 60° per second. Isometric tests for elbow-flexion and -extension were performed with angles of 47° and 93°, isokinetic testing ranging from 0° to 140° in the elbow joint, and speed set to 30°/s. Shoulder rotation was measured at −23° and 23° isometrically, and −25° to 70° dynamically with the dynamometer allowing a speed of 30°/s. Seat-position, dynamometer-position, and -arm-length were recorded at the first test to allow for adequate re-testing. The same order of tests was performed for each patient at T0 and T2.
The rate of perceived exertion was recorded for every exercise as well as the number of repetitions and resistance. Patients were shown a visual analog scale including percentage scaling from 0 to 100%, the RPE-scale by Borg/Noble modified by Fiehn/Schulte-Frei.
QoL was assessed using the questionnaire EORTC QLQ-C30, Version 3.0, validated by the European Organization for Research and Treatment of Cancer [23, 24]. Furthermore, the Freiburger Fragebogen zur körperlichen Aktivität, validated by the University Clinic Freiburg [25], was used to assess patients’ physical activity besides the intervention. The questionnaires were completed at T0, T1, and T2.
Safety
The physical status and adverse events were recorded by the therapists during each session. Spontaneously reported adverse events or those observed by the therapists were also recorded.
Statistical Analysis
The changes from baseline (T0) to T1 and T2 were computed. Intergroup differences were analyzed using the t test for equality of means. Missing data were excluded from the analysis; therefore, the sample size varied for the different measurements. All the results presented refer to the per-protocol analysis; patients with low levels of adherence were excluded from the analysis. Analyses were carried out using IBM SPSS Version 23.
Results
Overall, 40 patients participated in the study of whom 38 (IG: n = 19, CG: n = 19) completed all measurements. There was one drop-out in the intervention group because of the inability to be tested within the defined timeframe. One dropout in the CG was physically active for more than 2 h per week. No adverse events were reported. The baseline patient characteristics are shown in Table 2. There were no significant intergroup differences at baseline.
. | Intervention group . | Control group . |
---|---|---|
Size | N = 20 | N = 20 |
Average age (range) | 48, 55 (28–68) | 47, 35 (25–68) |
Mean height | 167, 8 cm | 167, 35 |
Mean BMI | 22, 79 | 24, 69 |
Stadium UICC | 2 × 0 | 2 × 0 |
11 × I | 9 × I | |
5 × II | 8 × II | |
2 × III | 1 × IV | |
Type of surgery | 5 mastectomy, 15 breast-conserving | 3 mastectomy, 17 breast-conserving |
Experienced in resistance training | 10 | 12 |
. | Intervention group . | Control group . |
---|---|---|
Size | N = 20 | N = 20 |
Average age (range) | 48, 55 (28–68) | 47, 35 (25–68) |
Mean height | 167, 8 cm | 167, 35 |
Mean BMI | 22, 79 | 24, 69 |
Stadium UICC | 2 × 0 | 2 × 0 |
11 × I | 9 × I | |
5 × II | 8 × II | |
2 × III | 1 × IV | |
Type of surgery | 5 mastectomy, 15 breast-conserving | 3 mastectomy, 17 breast-conserving |
Experienced in resistance training | 10 | 12 |
Primary Endpoint
Strength: Mean torque, consisting of the maximum values of six measurements (four isometric and two isokinetic), per joint movement was analyzed. There were significant intergroup differences (p = 0.001) in the maximum torque in both legs. Maximum torque improved between 11.91 and 12.94% in the IG. In this regard, decreases of 1.59–1.97% in the CG were recorded. Significant intergroup differences in elbow flexion and extension were detected on both sides (p = 0.001). Intergroup differences in shoulder rotation were significant for left arms (p = 0.021) and right arms (p = 0.029). The IG improved in all strength measurements (mean changes from 6.85 to 13.07%) whereas the CG showed decreased values in all measurements at T2 (1.59–6.74%) as shown in Table 3. All 20 patients in the IG completed the target of at least 20 training sessions with a mean of 21 sessions. The average adherence was 87.5%.
Outcome . | Time point . | N . | p value (intergroup) . | Mean change IG (standard deviation) . | Percentage mean change . | Mean change CG (standard deviation) . | Percentage mean change . |
---|---|---|---|---|---|---|---|
Knee flexion-extension | |||||||
Left | T2-T0 | 18 | 0.000 | 67.8 (51.3) | 11.91 | −14.6 (59.6) | −1.97 |
Right | T2-T0 | 18 | 0.000 | 73 (62.4) | 12.94 | −16.3 (60.6) | −1.59 |
Elbow flexion-extension | |||||||
Left | T2-T0 | 19 | 0.001 | 25.4 (21.3) | 13.07 | −21.2 (49.4) | −5.72 |
Right | T2-T0 | 19 | 0.001 | 15.3 (20.1) | 7.51 | −9.7 (20.6) | −4.15 |
Shoulder rotation | |||||||
Left | T2-T0 | 19 | 0.021 | 10.5 (15.8) | 6.85 | −3.6 (19.1) | −2.15 |
Right | T2-T0 | 19 | 0.029 | 12.9 (25.2) | 7.87 | −5.8 (23.9) | −6.74 |
Outcome . | Time point . | N . | p value (intergroup) . | Mean change IG (standard deviation) . | Percentage mean change . | Mean change CG (standard deviation) . | Percentage mean change . |
---|---|---|---|---|---|---|---|
Knee flexion-extension | |||||||
Left | T2-T0 | 18 | 0.000 | 67.8 (51.3) | 11.91 | −14.6 (59.6) | −1.97 |
Right | T2-T0 | 18 | 0.000 | 73 (62.4) | 12.94 | −16.3 (60.6) | −1.59 |
Elbow flexion-extension | |||||||
Left | T2-T0 | 19 | 0.001 | 25.4 (21.3) | 13.07 | −21.2 (49.4) | −5.72 |
Right | T2-T0 | 19 | 0.001 | 15.3 (20.1) | 7.51 | −9.7 (20.6) | −4.15 |
Shoulder rotation | |||||||
Left | T2-T0 | 19 | 0.021 | 10.5 (15.8) | 6.85 | −3.6 (19.1) | −2.15 |
Right | T2-T0 | 19 | 0.029 | 12.9 (25.2) | 7.87 | −5.8 (23.9) | −6.74 |
We measured the rate of perceived exertion (range 0–100) for every exercise at every training session. The mean RPE was 91.87.
Figure 1 shows the mean RPE for each of the first 20 training sessions (n = 20) and the mean indexed weights for all exercises in one training session. A target RPE of 90+ was reached at the fifth training session, whereas the mean resistance increased over the course of all 20 training sessions. The minimum and maximum values fluctuated strongly in the first training sessions and showed the smallest amplitudes in training sessions 12 and 13.
Figure 2 shows the development of mean RPE and resistance in patients with a change in medication during the 10th–12th training session (n = 15). After steady progress throughout the first weeks of exercise, the mean resistance stalls with the change in cytotoxics. Subgroup 1 received docetaxel during the second half of treatment.
Figure 3 shows the development of mean RPE and resistance for patients during mono-chemotherapy, who received the same cytotoxic throughout all training sessions (n = 5). The mean resistance peaked at the 20th session, while the mean RPE was consistently above 94 beginning with the 8th training session. The mean resistance and mean RPE were higher than those in subgroup 1. The smaller sample size led to fewer fluctuations in the results.
Table 4 illustrates the levels of the mean RPE and indexed resistance/weights in relation to the time of the last treatment. The mean resistance was highest at 16–22 days after the administration of chemotherapy (88.98). The highest mean RPE was recorded in the same timeframe (93.34). 9–15 days into the chemotherapy cycle, patients showed the lowest mean resistance index, although the mean RPE was 90.95, which is comparable to the results of 1 day into the cycle.
Interval: days after administration of chemotherapy . | 1 . | 2–5 . | 2–8 . | 9–15 . | 16–22 . |
---|---|---|---|---|---|
N | 30 | 63 | 153 | 147 | 90 |
Mean RPE | 90.90 | 92.05 | 92.62 | 90.95 | 93.34 |
Mean resistance index | 87.19 | 85.76 | 85.84 | 85.08 | 88.98 |
Interval: days after administration of chemotherapy . | 1 . | 2–5 . | 2–8 . | 9–15 . | 16–22 . |
---|---|---|---|---|---|
N | 30 | 63 | 153 | 147 | 90 |
Mean RPE | 90.90 | 92.05 | 92.62 | 90.95 | 93.34 |
Mean resistance index | 87.19 | 85.76 | 85.84 | 85.08 | 88.98 |
Due to the study design, there was no training 1 day after baseline so that the results from the first circle (habituation phase) had an impact on the overall results. Table 5 shows the mean RPE and mean resistance index in relation to treatment after the second dose of cytotoxic chemotherapy within the study. The highest values for the mean resistance index and mean RPE were recorded 16–22 days after treatment. Mean resistance index was the lowest at 2–5 days after treatment.
Interval: days after administration of chemotherapy . | 1 . | 2–5 . | 2–8 . | 9–15 . | 16–22 . |
---|---|---|---|---|---|
N | 30 | 61 | 144 | 117 | 69 |
Mean RPE | 90, 90 | 92, 71 | 93, 65 | 93, 29 | 94, 82 |
Mean resistance index | 87, 19 | 86, 86 | 87, 36 | 89, 14 | 92, 96 |
Interval: days after administration of chemotherapy . | 1 . | 2–5 . | 2–8 . | 9–15 . | 16–22 . |
---|---|---|---|---|---|
N | 30 | 61 | 144 | 117 | 69 |
Mean RPE | 90, 90 | 92, 71 | 93, 65 | 93, 29 | 94, 82 |
Mean resistance index | 87, 19 | 86, 86 | 87, 36 | 89, 14 | 92, 96 |
Figure 4 shows mean RPE and resistance in relation to days since treatment and cycle of treatment. Training weights were increased within each cycle and had to be reduced in the first few days after each treatment. The resistance applied was higher with every circle completed compared to the corresponding timeframe in the previous cycles.
Secondary Endpoints
QoL: There were several intergroup differences in EORTC QLQ-C30 scores. The global QoL differed significantly between T0 and T2 with an increase of 7.5 in the IG and a decrease of 13.5 points in the CG. Physical functioning between T0-T1 (p = 0.039) and T0-T2 (p = 0.002) was significant. Between T0 and T1, the IG improved by an average of 5.6 points whereas the CG’s physical functioning decreased by 10.1 points. Between T0 and T2, the IG improved by an average of 6.3 Points, the CG showed decreased values by 20.3 points. Intergroup emotional functioning was significant (p = 0.017) between T0 and T2 with an increase of 6.1 points in the IG and a decrease of 7.9 points in the CG. Cognitive functioning showed significant intergroup differences between T0 and T1 (p = 0.043). The IG displayed an increase in cognitive functioning of 12.3 points, and the CG lost an average of 2.6 points. Improvements in insomnia (T0–T1, p = 0.076), constipation (T1–T2, p = 0.066), and role functioning (T1–T2, p = 0.071) showed strong tendencies.
No other functioning or symptom scale scores were significant. All measurements are documented in Table 6.
. | . | . | . | IG . | CG . |
---|---|---|---|---|---|
Sample size | T0 | N | 20 | 20 | |
T1 | N | 20 | 20 | ||
T2 | N | 19 | 19 |
. | . | . | . | IG . | CG . |
---|---|---|---|---|---|
Sample size | T0 | N | 20 | 20 | |
T1 | N | 20 | 20 | ||
T2 | N | 19 | 19 |
Outcome . | Time point . | N . | p value (intergroup) . | Mean change (standard deviation) . | Mean change (standard deviation) . |
---|---|---|---|---|---|
EORTC QLQ-C30 (Scale 0–100) | |||||
QoL | T2-T0 | 19 | 0.032 | 7.5 | −13.6 |
29.9 | 28.1 | ||||
T2-T1 | 19 | 0.063 | −1.7 | −18.4 | |
18.1 | 33.3 | ||||
T1-T0 | 19 | 0.618 | 9.2 | 4.8 | |
29.4 | 24.1 | ||||
Physical functioning | T2-T0 | 19 | 0.002 | 6.3 | −20.3 |
29 | 20.4 | ||||
T2-T1 | 19 | 0.131 | 0.7 | −10.2 | |
20.7 | 22.6 | ||||
T1-T0 | 19 | 0.039 | 5.6 | −10.1 | |
22.3 | 22.9 | ||||
Role functioning | T2-T0 | 19 | 0.317 | 2.6 | 9.6 |
44.5 | 26.2 | ||||
T2-T1 | 19 | 0.071 | 1.8 | −17.5 | |
29.9 | 34 | ||||
T1-T0 | 19 | 0.558 | 2.6 | 9.6 | |
44.5 | 26.2 | ||||
Emotional functioning | T2-T0 | 19 | 0.017 | 6.1 | −7.9 |
30.4 | 23.3 | ||||
T2-T1 | 19 | 0.442 | −0.9 | −6.6 | |
24 | 21.1 | ||||
T1-T0 | 19 | 0.119 | 6.1 | −7.9 | |
30.4 | 23.3 | ||||
Cognitive functioning | T2-T0 | 19 | 0.257 | 12.3 | −2.6 |
23.5 | 20.2 | ||||
T2-T1 | 19 | 0.784 | −12.3 | −9.6 | |
26.6 | 32.1 | ||||
T1-T0 | 19 | 0.043 | 12.3 | −2.6 | |
23.5 | 20.2 | ||||
Social functioning | T2-T0 | 19 | 0.176 | 12.3 | 0 |
31.3 | 22.9 | ||||
T2-T1 | 19 | 0.918 | 0.9 | 1.8 | |
26.9 | 25.4 | ||||
T1-T0 | 19 | 0.145 | 11.4 | −1.8 | |
33.8 | 18.3 | ||||
Fatigue | T2-T0 | 19 | 0.214 | −8.8 | 3.5 |
26.6 | 32.9 | ||||
T2-T1 | 19 | 0.315 | −0.9 | 9.4 | |
21.1 | 38.4 | ||||
T1-T0 | 19 | 0.780 | −7.9 | −5.8 | |
23.4 | 21.4 | ||||
Nausea and vomiting | T2-T0 | 19 | 0.628 | −18.4 | −14.9 |
23.5 | 20.7 | ||||
T2-T1 | 19 | 0.616 | −9.6 | −5.3 | |
24.4 | 28.9 | ||||
T1-T0 | 19 | 0.905 | −8.8 | −9.6 | |
21.8 | 23.1 | ||||
Pain | T2-T0 | 19 | 0.574 | 8.8 | 17.5 |
51.6 | 43.2 | ||||
T2-T1 | 19 | 0.649 | 19.3 | 13.2 | |
39.8 | 42.5 | ||||
T1-T0 | 19 | 0.199 | −10.5 | 4.4 | |
43.5 | 24.1 | ||||
Dyspnea | T2-T0 | 19 | 1 | 5.3 | 5.3 |
33.8 | 46.2 | ||||
T2-T1 | 19 | 0.881 | 5.3 | 7 | |
29.9 | 40.9 | ||||
T1-T0 | 19 | 0.824 | 0 | −1.8 | |
27.2 | 20.7 | ||||
Insomnia | T2-T0 | 19 | 0.791 | 14 | 17.5 |
39 | 42.1 | ||||
T2-T1 | 19 | 0.240 | 17.5 | 3.5 | |
35.8 | 36.7 | ||||
T1-T0 | 19 | 0.076 | −3.5 | 14 | |
24.6 | 33.9 | ||||
Appetite loss | T2-T0 | 19 | 0.269 | −21.1 | −5.3 |
44.7 | 42 | ||||
T2-T1 | 19 | 0.671 | 0 | −5.3 | |
38.5 | 37.3 | ||||
T1-T0 | 19 | 0.102 | −21.1 | 0 | |
38.8 | 38.5 | ||||
Constipation | T2-T0 | 19 | 0.143 | −21.1 | −3.5 |
37.2 | 35 | ||||
T2-T1 | 19 | 0.066 | −10.5 | 8.8 | |
35.2 | 26.9 | ||||
T1-T0 | 19 | 0.901 | −10.5 | −12.3 | |
52.2 | 31.8 | ||||
Diarrhea | T2-T0 | 19 | 1 | 8.8 | 8.8 |
31.1 | 24.4 | ||||
T2-T1 | 19 | 0.424 | 7 | 0 | |
21 | 31.4 | ||||
T1-T0 | 19 | 0.419 | 1.8 | 8.8 | |
20.7 | 31.1 | ||||
Financial difficulties | T2-T0 | 19 | 0.115 | −5.3 | 5.3 |
25.5 | 12.5 | ||||
T2-T1 | 19 | 0.574 | 0 | −3.5 | |
19.2 | 18.9 | ||||
T1-T0 | 19 | 0.046 | −5.3 | 8.8 | |
22.9 | 18.7 |
Outcome . | Time point . | N . | p value (intergroup) . | Mean change (standard deviation) . | Mean change (standard deviation) . |
---|---|---|---|---|---|
EORTC QLQ-C30 (Scale 0–100) | |||||
QoL | T2-T0 | 19 | 0.032 | 7.5 | −13.6 |
29.9 | 28.1 | ||||
T2-T1 | 19 | 0.063 | −1.7 | −18.4 | |
18.1 | 33.3 | ||||
T1-T0 | 19 | 0.618 | 9.2 | 4.8 | |
29.4 | 24.1 | ||||
Physical functioning | T2-T0 | 19 | 0.002 | 6.3 | −20.3 |
29 | 20.4 | ||||
T2-T1 | 19 | 0.131 | 0.7 | −10.2 | |
20.7 | 22.6 | ||||
T1-T0 | 19 | 0.039 | 5.6 | −10.1 | |
22.3 | 22.9 | ||||
Role functioning | T2-T0 | 19 | 0.317 | 2.6 | 9.6 |
44.5 | 26.2 | ||||
T2-T1 | 19 | 0.071 | 1.8 | −17.5 | |
29.9 | 34 | ||||
T1-T0 | 19 | 0.558 | 2.6 | 9.6 | |
44.5 | 26.2 | ||||
Emotional functioning | T2-T0 | 19 | 0.017 | 6.1 | −7.9 |
30.4 | 23.3 | ||||
T2-T1 | 19 | 0.442 | −0.9 | −6.6 | |
24 | 21.1 | ||||
T1-T0 | 19 | 0.119 | 6.1 | −7.9 | |
30.4 | 23.3 | ||||
Cognitive functioning | T2-T0 | 19 | 0.257 | 12.3 | −2.6 |
23.5 | 20.2 | ||||
T2-T1 | 19 | 0.784 | −12.3 | −9.6 | |
26.6 | 32.1 | ||||
T1-T0 | 19 | 0.043 | 12.3 | −2.6 | |
23.5 | 20.2 | ||||
Social functioning | T2-T0 | 19 | 0.176 | 12.3 | 0 |
31.3 | 22.9 | ||||
T2-T1 | 19 | 0.918 | 0.9 | 1.8 | |
26.9 | 25.4 | ||||
T1-T0 | 19 | 0.145 | 11.4 | −1.8 | |
33.8 | 18.3 | ||||
Fatigue | T2-T0 | 19 | 0.214 | −8.8 | 3.5 |
26.6 | 32.9 | ||||
T2-T1 | 19 | 0.315 | −0.9 | 9.4 | |
21.1 | 38.4 | ||||
T1-T0 | 19 | 0.780 | −7.9 | −5.8 | |
23.4 | 21.4 | ||||
Nausea and vomiting | T2-T0 | 19 | 0.628 | −18.4 | −14.9 |
23.5 | 20.7 | ||||
T2-T1 | 19 | 0.616 | −9.6 | −5.3 | |
24.4 | 28.9 | ||||
T1-T0 | 19 | 0.905 | −8.8 | −9.6 | |
21.8 | 23.1 | ||||
Pain | T2-T0 | 19 | 0.574 | 8.8 | 17.5 |
51.6 | 43.2 | ||||
T2-T1 | 19 | 0.649 | 19.3 | 13.2 | |
39.8 | 42.5 | ||||
T1-T0 | 19 | 0.199 | −10.5 | 4.4 | |
43.5 | 24.1 | ||||
Dyspnea | T2-T0 | 19 | 1 | 5.3 | 5.3 |
33.8 | 46.2 | ||||
T2-T1 | 19 | 0.881 | 5.3 | 7 | |
29.9 | 40.9 | ||||
T1-T0 | 19 | 0.824 | 0 | −1.8 | |
27.2 | 20.7 | ||||
Insomnia | T2-T0 | 19 | 0.791 | 14 | 17.5 |
39 | 42.1 | ||||
T2-T1 | 19 | 0.240 | 17.5 | 3.5 | |
35.8 | 36.7 | ||||
T1-T0 | 19 | 0.076 | −3.5 | 14 | |
24.6 | 33.9 | ||||
Appetite loss | T2-T0 | 19 | 0.269 | −21.1 | −5.3 |
44.7 | 42 | ||||
T2-T1 | 19 | 0.671 | 0 | −5.3 | |
38.5 | 37.3 | ||||
T1-T0 | 19 | 0.102 | −21.1 | 0 | |
38.8 | 38.5 | ||||
Constipation | T2-T0 | 19 | 0.143 | −21.1 | −3.5 |
37.2 | 35 | ||||
T2-T1 | 19 | 0.066 | −10.5 | 8.8 | |
35.2 | 26.9 | ||||
T1-T0 | 19 | 0.901 | −10.5 | −12.3 | |
52.2 | 31.8 | ||||
Diarrhea | T2-T0 | 19 | 1 | 8.8 | 8.8 |
31.1 | 24.4 | ||||
T2-T1 | 19 | 0.424 | 7 | 0 | |
21 | 31.4 | ||||
T1-T0 | 19 | 0.419 | 1.8 | 8.8 | |
20.7 | 31.1 | ||||
Financial difficulties | T2-T0 | 19 | 0.115 | −5.3 | 5.3 |
25.5 | 12.5 | ||||
T2-T1 | 19 | 0.574 | 0 | −3.5 | |
19.2 | 18.9 | ||||
T1-T0 | 19 | 0.046 | −5.3 | 8.8 | |
22.9 | 18.7 |
Discussion
The aim of our study was to implement an adaptive, progressive, supervised resistance protocol for BCPs during chemotherapy, improving muscle strength, physical condition and overall QoL while reducing therapy-induced side-effects. Although a growing number of studies examined the effects of different forms and intensities of physical activity, the dosage and type for individual patients remain unclear [9]. Resistance-only studies of BCP undergoing chemotherapy are scarce [17, 26]. Consistent with the aim of our study, patients in the IG benefited from the adaptive, progressive, and supervised intervention. We reported highly significant intergroup differences in all strength parameters and in different subscales of the EORTC QLQ-C30. We also documented a cyclic performance level in relation to days since chemotherapy.
Our findings document that the number of days since treatment must be considered when conducting training sessions. Differences in subgroups of patients with different medications suggest that training protocols must be designed with close regard to medical treatment.
The range of training values varies greatly, illustrating the impact of the form of the day and motivational factors. Under these circumstances, skilled and experienced trainers and therapists are a necessity for successful training control. The warm-up set before each exercise can help assess the form of the day.
The strengths of the study are close monitoring in one-on-one training sessions and maintaining adequate loads in each phase of treatment by utilizing a simple form of training control (RPE-Scale). Psychosocial effects as a potential bias were not recorded but were minimized by rotating trainers and patients. Strength training and measurements were performed using different machines to prevent habituation. Strength tests and questionnaires were carried out within a strict timeframe of 5–10 days after treatment for better comparability. The use of EMG-measurements proved to be helpful especially during isometric measurements in inexperienced patients. We used the added values of six maximum tests (four isometric and two isokinetic movements) to compensate for difficulties in execution and to capture muscular strength in different positions. Flexibility in scheduling and the adaptive design of the training protocol have potentially led to a high level of adherence to a study during chemotherapy.
However, there are potential limitations to the study: the small sample size, single-center design and the lack of randomization have to be mentioned, although IG and CG proved to be comparable in many categories. Yet the practicability of the level of intense screening and supervision in larger, clinical studies is doubtful. Furthermore, there is still an evident lack of training control, adaptive intensity and reliability in current study designs. Therefor our findings remain relevant for the design and execution of new studies and the implementation of state-of-the-art care.
75% of the IG were in a treatment protocol with a change in cytotoxic drugs during the study. Hence, the effects of different medications on physical performance remain unclear. Our findings suggest that the resistance levels during training stagnated after the change in medication.
Future studies should further evaluate the appropriate dosage and form of physical activity for each patient between the individual areas of treatment, motivation, experience, interests, and comorbidities building on the findings of Courneya [22], implementing means of training control and periodization. Exercise therapy can benefit from our findings by implementing simple mechanisms of training control to compensate for the form of the day and using adequate loads in accordance with the study aims. Using these mechanisms, patients can be empowered to better estimate their own capacity and motivated by adaptive and realistic resistance settings. Larger studies could lead to individualized guidelines for adaptive training in acute therapy and for the heterogenous group in clinical practice [27].
De Backer et al. [28] documented sustained long-term effects of strength training during different phases of therapy on muscle strength, cardiopulmonary function, HRQOL, and fatigue. Follow-up studies should also analyze sustained training motivation after intervention and if the return to work (especially in younger patients) can be shortened by resistance interventions.
Individualization, documentation but also modern equipment and techniques (e.g., excentric resistance machines) can lead to higher motivation and consequently better compliance, making long-term-effects more likely. These techniques can also help with the challenges of supervision, relieving therapists in implementation. We suggest that guidelines for BC rehabilitation should include adaptive high-intensity resistance training. Further studies should use adaptive training protocols to apply the target-intensity in each session.
Conclusion
BCPs experience numerous side-effects during and after treatment. There is sufficient evidence for the efficacy of training interventions in adjuvant therapy including sole resistance training protocols. However, individualized training guidelines in the supportive care of BCPs, taking factors into account such as medication, fitness, and form of the day are still under development. Adaptive resistance training with simple training control mechanisms proved to be effective regarding optimal intensity in each training session.
Acknowledgments
We would like to thank the patients who participated in this study and the involved physicians and nurses, especially Anke Schmitz. We also thank the German Sports University Cologne for providing the testing facilities and Birgit Schulte-Frei and the Team at ProPhysio Köln for the isokinetic testing facilities and the training center; Sabine Latta and all physicians involved at the Breast Center of the University Hospital Cologne; Alexander Schenk and Philipp Zimmer for their laboratory work; Diana Mäurer, Jule Wolf, Anna Gerhard, Tobias Borchers, Steffen Overkämping, and Sarah Starck for training assistance.
Statement of Ethics
Ethics approval was obtained from the University Hospital of Cologne, approval number (10-170). All patients provided written informed consent for treatment and prospective data collection in accordance with the Declaration of Helsinki.
Conflict of Interest Statement
The authors declare that they have no conflicts of interest. The results have been partially presented at the following conferences: German Cancer Society Conference 2012, 2014, 2018, German Society of Hematology and Oncology Conference 2017, and German Society of Sports Medicine and Prevention 2012, 2014.
Funding Sources
This study was received support grant from Stiftung Integrierte Medizin, Otto-Seeling-Promenade 2-4, D-90762 Fürth, Germany to the senior author (FB).
Author Contributions
Conceptualization: L.G., F.T.B., S.F., W.M., N.H., and W.B.; methodology: L.G., S.F., and F.T.B.; investigation: L.G. and S.F.; statistical analysis: R.K., L.G., and S.F.; and writing: L.G. and F.T.B.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.