Download Randomized Trial of a Physical Activity Intervention in Women With

Original Article
Randomized Trial of a Physical Activity Intervention in Women
With Metastatic Breast Cancer
Jennifer A. Ligibel, MD1; Anita Giobbie-Hurder, MS2; Laura Shockro, BS1; Nancy Campbell, MEP1;
Ann H. Partridge, MD, MPH1; Sara M. Tolaney, MD, MPH1; Nancy U. Lin, MD1; and Eric P. Winer, MD1
BACKGROUND: Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors’ knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer. METHODS: Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity
exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per
week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview,
and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire. RESULTS: A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and
approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P 5 .15). Women randomized to the exercise intervention experienced a nonsignificant
increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P 5 .17) and physical functioning (EORTC QLQ
C30: 4.79 vs 0.93 [P 5 .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P 5 .35]) compared with control participants. CONCLUSIONS: Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women
with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help
C 2016
women with metastatic disease live more fully with fewer symptoms from disease and treatment. Cancer 2016;122:1169-77. V
American Cancer Society.
KEYWORDS: breast cancer, exercise, metastatic, physical function, quality of life.
INTRODUCTION
Over the past decade, the benefits of exercise have increasingly been demonstrated for women with early breast cancer.
Several observational studies have indicated that women who engage in regular exercise after a diagnosis of stage I to III
breast cancer experience a lower risk of breast cancer recurrence and related mortality.1-3 In addition, >100 interventional
trials have been conducted in women with early-stage breast cancer.4-6 Although no trial to date has been large enough to
test the impact of increased exercise on cancer-related outcomes, these studies have demonstrated that exercise is safe and
provides several health benefits in patients with breast cancer both during and after adjuvant therapy.
Despite these data in women with early-stage breast cancer, to our knowledge there is little information regarding
the feasibility or benefits of exercise in women with advanced breast cancer. With new treatments, women often live several
years after a diagnosis of metastatic breast cancer. However, during this time, many women experience significant side
effects from breast cancer treatment, as well as symptoms from their disease. Fatigue, poor physical functioning, pain, and
other symptoms can impair a woman’s ability to complete activities of daily living in the years after the diagnosis of metastatic breast cancer, which in turn significantly compromises quality of life (QOL) and mood. Interventions are needed to
help alleviate symptoms and allow women to continue to function normally in the years that they survive with advanced
breast cancer.
Corresponding author: Jennifer A. Ligibel, MD, Breast Oncology Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Yawkey 1234,
Boston, MA 02215; Fax: (617) 632-1930; [email protected]
1
Breast Oncology Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; 2Department of Statistics and Computation Biology,
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
These data have been previously presented in part at the 2012 Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012; Chicago, IL.
DOI: 10.1002/cncr.29899, Received: October 22, 2015; Revised: December 21, 2015; Accepted: December 28, 2015, Published online February 12, 2016 in Wiley
Online Library (wileyonlinelibrary.com)
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April 15, 2016
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Original Article
The Metastatic Exercise Training Trial was designed
to study the impact of a moderate-intensity aerobic exercise intervention on physical functioning in women with
metastatic breast cancer. The study’s primary objective
was to assess the impact of the intervention on objective
and subjective measures of physical functioning, as measured through a treadmill test and questionnaire, respectively. Secondary aims included examining the impact of
the intervention on QOL, anxiety and depression, fatigue,
and exercise behaviors.
MATERIALS AND METHODS
Study Population
Participants were recruited from the Breast Oncology
Center at the Dana-Farber Cancer Institute and from the
Beth Israel Deaconess Medical Center, both in Boston,
between September 2006 and March 2011. Eligibility criteria included having metastatic breast cancer or locally
advanced disease not amenable to surgical resection, a life
expectancy of 12 months, baseline performance of
150 minutes of recreational physical activity per week,
and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients were excluded if they had
untreated brain metastases, uncontrolled cardiac disease,
or other contraindications to moderate-intensity exercise.
Patients with bony metastatic disease were allowed to
participate in the study.
Medical clearance was obtained from all participants’ medical oncologists or primary care providers. The
study was approved by the Institutional Review Board at
the Dana-Farber/Harvard Cancer Center and registered
on the clinicaltrials.gov Web site (NCT00405782).
Informed consent was obtained from all participants
before enrollment.
Study Design
After enrollment, participants were randomized 1:1 to an
exercise intervention group or wait-list control group.
The intervention group participated in a 16-week supervised and home-based aerobic exercise intervention. The
control group received routine care for 16 weeks and was
then offered participation in the exercise intervention.
Subjects were stratified by current treatment (endocrine
therapy vs chemotherapy/biologic therapy) and the presence of visceral metastatic disease (yes vs no). Assessment
of weekly minutes of physical activity, cardiorespiratory
fitness, self-reported physical functioning, QOL, anxiety,
depression, and fatigue was performed at baseline and after the completion of the 16-week study period. Changes
in these measures over time were compared between par1170
ticipants randomized to the intervention and control
groups.
Exercise Intervention
The exercise intervention was a 16-week, moderate-intensity aerobic exercise program, based on a program previously piloted in women with early-stage breast cancer
undergoing adjuvant chemotherapy that had resulted in
significant increases in physical activity and improvements in fitness and physical functioning.7 The intervention was delivered through a series of in-person and
telephone contacts by an exercise physiologist. In-person
meetings occurred weekly throughout the first month of
the study and monthly thereafter, supplemented by
weekly telephone contacts. Sessions focused on building
exercise self-efficacy, overcoming barriers to exercise,
documenting any injuries, and reviewing safe exercise
practices. The target goal was 150 minutes of moderateintensity exercise per week.
Each participant was provided with a heart rate
monitor, a pedometer, and an exercise journal to record
the number of minutes of exercise performed each week,
the average heart rate during exercise, and the number of
daily steps. Exercise journals were reviewed with the exercise physiologist each week. Finally, participants were provided with a 16-week membership to a gym in their local
area.
Measurements
Demographic data and disease and treatment information
were collected at the time of participant enrollment. Study
measures were collected at baseline and at the end of the
16-week study period. Physical functioning was assessed
through the Physical Functioning subscale of the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire Core 30 (EORTC QLQC30) questionnaire, a 5-item scale that assesses an individual’s ability to complete activities of daily living as well as
more strenuous physical tasks. This subscale has been
used in previous trials of exercise interventions in cancer
populations8 and is sensitive to changes over time in functional status from prechemotherapy to 8 days after chemotherapy in the expected directions in patients with breast
cancer.9,10
Cardiorespiratory fitness was assessed through the
modified Bruce Ramp Treadmill test. The test began at a
speed of 2.0 miles per hour and no elevation, and the
speed and elevation were then slowly increased until the
participant reached 85% of the maximum age-predicted
maximum heart rate or requested that the test be stopped.
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Exercise Intervention in Metastatic Breast Cancer/Ligibel et al
The Bruce Ramp protocol was chosen for the current
study because the work rate increases in a constant and
continuous manner,11-13 which is well suited for patients
with comorbidities.
Participants also underwent evaluation of exercise
behaviors, QOL, and fatigue at baseline and at the end of
the 16-week study period. Exercise behaviors were measured with the 7-day Physical Activity Recall interview, an
interviewer-administered instrument that has been demonstrated to correlate with changes in maximal oxygen
uptake, body composition,14-16 and activity patterns generated through direct observation or activity monitors.16,17 Interviews were conducted over the telephone by
a member of the study staff who was blinded to the intervention assignment.
Fatigue was assessed with the Functional Assessment
of Chronic Illness Therapy (FACIT)-Fatigue scale, a 13item scale designed to assess fatigue in terms of its intensity and interference with performing everyday functions.18,19 QOL and symptom measures were assessed
through the EORTC QLQ-C30. Compliance with the
exercise intervention was assessed in women randomized
to exercise through evaluation of weekly exercise journals
and through monitoring attendance at supervised exercise
sessions and telephone calls. Safety was assessed through
queries regarding adverse events during supervised
exercise sessions and telephone contacts with study
participants.
Statistical Analysis
The primary objectives of the current study were to assess
the 16-week changes in 1) physical functioning scores as
measured by the EORTC QLQ-C30 instrument and 2)
cardiorespiratory fitness as measured by the Bruce Ramp
Treadmill test. Secondary objectives included assessments
of changes in fatigue (FACIT version 4); anxiety and
depression (Hospital Anxiety and Depression Scale);
QOL (EORTC QLQ-C30); physical activity levels
(7-day Physical Activity Recall); and, for women assigned
to the exercise arm, compliance with the exercise
intervention.
The study design assumed that 25% of women
would not complete the trial and an additional 5% of
women would cross over to the unassigned group. Therefore, 100 women would be required to enroll in the study
to have 70 women (approximately 35 per group) assessable for the primary endpoints. Based on Wilcoxon rank
sum tests with 2-sided significance levels of .05 for each
endpoint, there was 80% power to detect differences
between the intervention arms of 1) 18.6 in the physical
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April 15, 2016
functioning score and 2) 1.2 minutes in exercise tolerance,
given variability estimates of 22 minutes8 and 2.4
minutes,20 respectively, for changes in physical functioning and exercise tolerance.
Comparisons of baseline variables between the intervention arms to assess for imbalance used the Wilcoxon
rank sum test for continuous variables or the Fisher exact
test for categorical variables. Attrition rates in the intervention arms were compared using the Fisher exact test.
Given that unequal attrition rates were detected in the
study arms, analyses of primary endpoints were performed
using all available data and sensitivity analyses were performed using propensity score adjustments to the estimation of treatment effects of the 2 primary outcomes.
Covariates used in the logistic regression models to
estimate propensity scores were: race; ethnicity; Eastern
Cooperative Oncology Group performance status; menopausal status; presence of visceral metastatic disease; stratification variables; chemotherapy, hormonal therapy, and
biologic therapy recorded at baseline; years since the diagnosis of metastatic disease; age; baseline FACIT-Breast
Cancer; and baseline Hospital Anxiety and Depression
Scale.
The primary outcomes of changes in physical functioning and changes in exercise tolerance were estimated
using linear models with intervention assignment and
propensity score quartiles as predictors. Comparisons of
the exercise versus control groups were made using F tests.
Changes in secondary endpoints were compared between
intervention groups for available data using the Wilcoxon
rank sum test. All P values were 2-sided, with statistical
significance defined as P<.05. There were no corrections
for multiple comparisons.
Given the unexpected higher rate of study attrition
in the intervention arm, unplanned exploratory analyses
were performed in subsets of participants defined by baseline treatment (biologic therapy, chemotherapy, or endocrine therapy) to explore the feasibility of the exercise
intervention in patients receiving less-intensive treatments
for advanced breast cancer. Analyses of study primary
endpoints according to therapy subgroups are based on
linear models with intervention, therapy type, and their
interaction as predictors.
RESULTS
A total of 101 participants were enrolled in the protocol
(Fig. 1); 53 participants were randomized to the control
group and 48 to the exercise intervention. Imbalance in
the 2 arms was the result of block randomization. Baseline
data were available for 98 participants; 1 woman was
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Original Article
TABLE 1. Baseline Demographic, Disease, and Prior
Treatment Characteristics
Characteristic
Age (6 SD), y
Interval since diagnosis of
metastatic disease, y
Race
White
Black
Asian
ECOG performance status
0 (fully ambulatory)
1 (ambulatory/light work)
Missing data
Menopausal status
Pre/perimenopausal
Postmenopausal
Missing data
Visceral metastatic disease
Treatment at study entrya
Endocrine therapy
Chemotherapy
Biologic therapy
No treatment
Exercise
N 5 47
Control
N 5 51
49.3 (9.6)
2.2 (2.7)
50.7 (9.4)
1.7 (2.1)
47 (100%)
0 (0%)
0 (0%)
45 (88%)
5 (10%)
1 (2%)
38 (81%)
8 (17%)
1 (2%)
38 (74%)
12 (24%)
1 (2%)
11 (23%)
35 (74%)
1 (2%)
31 (66%)
18
32
1
34
25 (53%)
21 (45%)
16 (34%)
2 (4.3%)
27 (53%)
17 (33%)
20 (39%)
1 (2.0%)
(35%)
(63%)
(2%)
(67%)
Abbreviations: ECOG, Eastern Cooperative Oncology Group; SD, standard
deviation.
a
Some patients were receiving chemotherapy and biologic therapy at the
time of study entry.
found to be ineligible after randomization and 2 additional participants (1 of whom was randomized to the
intervention arm and 1 of whom was randomized to the
control arm) withdrew consent before the collection of
baseline measures. Baseline characteristics were distributed similarly in the exercise and control groups (Table
1). The majority of participants were white and had visceral metastatic disease. The average age of the participants was 49 years and the mean time between the
diagnosis of metastatic disease and study enrollment was
1.9 years. Approximately 53% of participants were being
treated with endocrine therapy at the time of study enrollment and the remaining patients were receiving treatment
with chemotherapy and/or biologic therapy.
Twenty-two patients withdrew consent and/or did
not complete the study (Fig. 1) and an additional 8
patients declined to undergo the final treadmill testing
but completed the intervention or control period and all
other study measures. Although there were no statistically
significant differences noted with regard to demographic
or treatment characteristics between patients who completed the protocol and those who dropped out, women
with longer durations of metastatic disease or who were
undergoing treatment with chemotherapy were less likely
to complete the study intervention. Participants assigned
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to the exercise intervention were more likely to drop out
of the study (14 participants vs 8 participants; P 5 .15)
and were more likely to decline the final treadmill testing
(6 participants vs 2 participants) compared with controls.
Physical Activity and Safety Outcomes
Baseline and 16-week physical activity data were available
for 98 and 76 participants, respectively (Table 2). At baseline, both groups were moderately active; control participants engaged in a mean of 79.2 6 84.3 minutes of
exercise per week and intervention participants engaged in
57.5 6 65.1 minutes of exercise per week (P 5 .29). Over
the 16-week study period, intervention participants
increased their minutes of exercise by a mean of 62.4 6
102.8 minutes per week versus 46.0 6 154.3 minutes per
week among controls (P 5 .17).
Adverse events were assessed by exercise trainers during the intervention period and by study staff during
study measurement visits. No injuries or other adverse
events were reported in intervention or control
participants.
Physical Functioning and Cardiorespiratory
Fitness
Self-reported physical functioning scores were available
from 98 participants at baseline and from 76 participants
at 16 weeks (Table 3). At baseline, both groups reported
relatively good physical functioning, with mean scores of
approximately 85 of 100. Analyses using all available data
demonstrated a nonsignificant improvement in physical
functioning in the intervention group versus controls at
16 weeks (change in intervention vs control group: 4.79
vs 0.93; P 5 .23). Results from propensity score modeling
were nearly identical to analyses using available data
(change in intervention vs control: 3.73; P 5 .25).
Results from Bruce Ramp Treadmill testing (Table
3) were available for 97 of 98 participants at baseline and
68 participants at 16 weeks, including 58% of women initially randomized to the intervention group and 80% of
women randomized to the control group (P 5 .017). At
baseline, average exercise tolerance was approximately 5.5
minutes in both groups. In analyses using all available
data, intervention participants increased their exercise duration by an average of 0.61 minutes compared with 0.37
minutes among control participants (P 5 .35). Propensity
score analysis demonstrated a smaller between-group difference in the duration of changes in the exercise test
(0.50 minutes vs 0.38 minutes; P 5 .64).
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Exercise Intervention in Metastatic Breast Cancer/Ligibel et al
Figure 1. Consolidated Standards Of Reporting Trials (CONSORT) diagram.
QOL and Patient-Reported Outcomes
Exploratory Analyses by Treatment
Participants completed QOL, fatigue, and exercise selfefficacy questionnaires at baseline and at 16 weeks (Table
4). At baseline, participants in both groups reported good
overall QOL and moderate levels of fatigue and exercise
self-efficacy. Participants in the intervention group reported
nonsignificant improvements in global QOL (6.0 6 17.5
vs -1.0 6 21.5; P 5 .17). There were no significant differences noted with regard to other outcomes between groups.
In unplanned analyses performed in subsets of participants defined by baseline treatment, the study attrition
rate was 8% in the group receiving biologic therapy, 34%
in the group receiving chemotherapy, and 18% in the
group receiving endocrine therapy (P 5 .13). Participants
in the chemotherapy group were less likely to complete
the final Bruce Ramp Treadmill test compared with the
other groups (55% in the chemotherapy group vs 84%
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Original Article
TABLE 2. Physical Activity Outcomesa
Baseline exercise, min/wk
Change in exercise over 16 wk, min/wk
Average no. of min of self-reported exercise per wk in journals
Exercise
Control
P
57.5 (65.1)
62.4 (102.8)
134.8 (138.3)
79.2 (84.3)
46.0 (154.3)
NA
.29
.17
NA
Abbreviation: NA, not applicable.
a
Data are expressed as the mean 6 the standard error.
TABLE 3. Baseline and Changes from Baseline in Bruce Ramp Treadmill and EORTC QLQ-C30 Physical
Functioning Assessments
Assessment
Exercise
EORTC QLQ-C30Physical Functioning
Baseline: mean (SD)
Bruce Ramp Treadmill, min
Available data
Propensity score
Baseline: mean (SD)
Available data
Propensity score
Control
Difference (95% CI)
84.0 (14.3)
85.1 (12.3)
Change from baseline: estimate (SE)
4.79 (2.4)
0.93 (2.1)
3.86 (22.4 to 10.2)
4.47 (2.6)
0.74 (2.2)
3.25 (22.7 to 10.2)
5.8 (1.8)
5.4 (1.7)
Change from baseline: estimate (SE)
0.61 (0.2)
0.37 (0.2)
0.24 (20.30 to 0.73)
0.50 (0.2)
0.38 (0.2)
0.12 (20.40 to 0.64)
Pa
.74
.23
.25
.21
.35
.64
Abbreviations: 95% CI, 95% confidence interval; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Core 30; SE, standard error.
a
P values for baseline comparisons were based on the Wilcoxon rank sum test; P values for changes from baseline were based on the F test of the linear
model.
and 77%, respectively, in the biologic therapy and endocrine therapy groups; P 5 .05).
The effect of the intervention on Bruce Ramp
Treadmill test times differed according to breast cancer
therapy (P 5 .003). Women in the exercise arm who were
treated with endocrine therapy had improvements in
treadmill times compared with women in the control
group (increase of 1.04 minutes vs 0.05 minutes); comparable improvements in the exercise arm were not noted for
women treated with chemotherapy or biologic therapy
(Table 5). There was no evidence that changes in selfreported functional status in response to the intervention
differed by cancer therapy group (P 5 .50). The impact of
the intervention on physical activity behaviors was also
not found to be significantly different between groups
(P 5 .36), but the intervention led to an increase of 74
minutes of exercise per week in intervention participants
receiving endocrine or no therapy versus controls in that
treatment group, whereas there was no increase in exercise
noted among intervention participants receiving biologic
therapy or chemotherapy compared with controls receiving those treatments.
DISCUSSION
In a group of women with metastatic breast cancer, adherence to a physical activity intervention, previously piloted
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in women with early-stage breast cancer undergoing adjuvant chemotherapy,7 was less than anticipated. Although
the intervention was primarily home-based, was individualized for each participant, and provided significant support for participants (including an exercise coach and
access to a local gym if desired), approximately 70% of the
women randomized to the exercise intervention completed the 16-week program, compared with 84% of
women randomized to the control group (P 5 .15). The
women who did complete the exercise intervention
increased their weekly exercise by 64.2 minutes per week
compared with an increase of 46.0 minutes per week in
the control group (P 5 .17).
To the best of our knowledge, the current study represents the largest trial to date evaluating the feasibility
and potential benefits of an exercise intervention in
women living with advanced breast cancer. The study
accrued 101 women with metastatic breast cancer over a
4.5-year period through a single institution, demonstrating that women living with advanced disease are potentially interested in lifestyle interventions. The results of
the current study also demonstrated that moderateintensity physical activity was safe in this study population, with no adverse events noted in the intervention
group, despite the finding that the majority of patients
had bony metastatic disease and many were receiving
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Exercise Intervention in Metastatic Breast Cancer/Ligibel et al
TABLE 4. EORTC QLQ-C30 Quality of Life Subscales and FACIT Fatigue: Baseline Measurements and
Changes from Baselinea
Intervention
Control
N 5 43
Exercise N 5 32
Assessment
EORTC QLQ-C30
Global QOL
Role functioning
Emotional functioning
Cognitive functioning
Social functioning
Fatigue
Nausea/vomiting
Pain
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
FACIT
Fatigue
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
Baseline
Change from
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
baseline
Mean
SD
Mean
SD
Wilcoxon Rank Sum P
67.2
6.0
79.7
2.6
74.2
9.6
90.6
3.1
77.1
7.8
33.0
23.8
5.2
2.1
24.5
1.0
15.6
26.3
33.3
211.5
13.5
23.1
14.6
26.3
8.3
9.4
19.4
17.5
21.1
21.2
17.1
18.7
19.4
23.0
28.0
22.0
22.3
21.4
7.8
11.0
21.2
20.3
18.9
23.1
23.9
34.5
22.2
28.5
25.3
21.5
16.9
19.4
71.5
21.0
80.6
21.2
71.1
3.4
81.4
5.4
74.4
20.4
33.9
1.6
5.0
0.4
23.6
24.7
13.5
4.0
40.3
27.8
9.3
0.8
10.1
20.0
15.5
21.6
20.2
21.5
23.0
21.0
20.1
19.2
30.3
32.5
26.3
27.1
17.3
27.5
13.9
18.4
21.3
20.4
18.1
19.8
31.3
28.9
19.7
21.2
20.0
20.6
22.2
25.1
.25
.17
.71
.35
.19
.16
.19
.38
.53
.09
.62
.63
.36
.75
.83
.22
.62
.04
.39
.22
.38
.62
.53
.21
.15
.05
37.0
2.7
10.8
8.4
36.0
2.7
10.3
9.3
.51
.63
Baseline
Change from baseline
Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; FACIT, Functional
Assessment of Chronic Illness Therapy; QOL, quality of life; SD, standard deviation.
a
Data were summarized as the mean (SD).
TABLE 5. Exploratory Analyses of Changes in Exercise Tolerance, Physical Functioning, and Physical Activity by Treatmenta
EORTC Physical Functioning
Exercise
Control
Difference
Bruce Ramp Treadmill, min
Exercise
Control
Difference
7-day PAR, min/wk
Exercise
Control
Difference
Biologic Therapy Only
N 5 11
Chemotherapy
N 5 26
Endocrine Therapy or
No Therapy
N 5 39
3.33 (6.9)
7.62 (5.2)
24.29 (229.5 to 20.9)
3.59 (3.8)
21.11 (4.0)
4.70 (211.4 to 20.8)
6.22 (3.5)
0.0 (2.8)
6.22 (27.0 to 19.4)
0.07 (0.5)
0.55 (0.4)
20.48 (22.4 to 1.4)
0.17 (0.3)
0.94 (0.3)
20.77 (22.2 to 0.4)
1.04 (0.3)
0.05 (0.2)
0.99 (0.05 to 1.9)
73.8 (88.9)
100.0 (67.3)
226.3 (2353 to 301)
29.6 (49.4)
44.7 (51.4)
254.3 (2263 to 155)
118.2 (45.0)
44.2 (36.3)
74.0 (298 to 246)
P
.56
.003
.36
Abbreviations: EORTC, European Organization for Research and Treatment of Cancer; PAR, Physical Activity Recall.
a
Unless otherwise indicated, estimates shown are the mean change (standard error) and are based on general linear models with intervention, therapy type,
and their interaction as predictors. P values are for the interaction of therapy by treatment.
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Original Article
chemotherapy. Unplanned analyses suggested that
women receiving less-intensive therapy, including those
receiving endocrine therapy alone or women undergoing
a break from treatment, were better able to participate in
the intervention, but this study overall did not demonstrate exercise to be a viable means with which to preserve
physical function or alleviate cancer-related or treatmentrelated symptoms in women with advanced cancer.
There is relatively little information regarding the
potential benefits of exercise in patients with metastatic
breast cancer. In contrast to the growing work demonstrating that women with early breast cancer who exercise
after diagnosis have a decreased risk of cancer-related and
overall mortality, to our knowledge there are no studies
examining the relationship between exercise and prognosis in patients with advanced breast cancer. There are also
few studies evaluating the feasibility or effects of an exercise intervention in women with metastatic breast cancer.
One study evaluated the impact of a seated exercise program, delivered through a commercially available DVD,
in 38 women initiating chemotherapy for metastatic
breast cancer and demonstrated that patients randomized
to the exercise intervention experienced a less significant
decline in their QOL compared with control participants.21 Another trial of 231 patients with metastatic disease, 20% of whom had breast cancer, demonstrated that
patients who were randomized to an 8-week supervised
exercise intervention experienced an improvement in
physical functioning but no change in fatigue compared
with participants randomized to a control intervention.22
It is interesting to note that attrition was high in both
studies, with only 75% of patients completing the seated
exercise trial, and 36% of participants in the exercise
group as well as 23% of control patients lost to follow-up
in the larger study.
Several weaknesses of the current study must be
acknowledged. As noted above, study attrition was greater
than expected and was unequal between the intervention
and control groups. Although changes in self-reported
and objective functional measures were in the expected
direction, thereby suggesting that exercise could potentially preserve physical functioning in women with metastatic breast cancer, the small sample size at 16 weeks
limited power for comparisons and the differential nature
of study attrition limits the generalizability of the current
study. In addition, despite the finding that participants
had advanced disease, QOL and physical functioning at
baseline were fairly high, making it more difficult to
detect changes as a result of the intervention. Participants
were also relatively active at baseline, and although there
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was a trend toward an increase in the minutes of physical
activity in the intervention group compared with controls,
especially among individuals treated with endocrine therapy, these differences were not statistically significant.
Finally, the population in the current study was heterogeneous, including women undergoing various forms of
therapy and at different points in the course of their metastatic disease. This contributed to the variation in changes
in physical activity and functional outcomes and limited
our power to detect changes in these endpoints. Future
studies are needed that focus on more homogenous
groups of women, especially women treated with endocrine therapy and those closer to the time of their initial
diagnosis of metastatic disease.
The current study enrolled 101 women who were on
average almost 2 years from the time of their diagnosis of
metastatic breast cancer to a study evaluating the impact
of a moderate-intensity, primarily home-based exercise
intervention on physical functioning and fitness. The
intervention was safe with no adverse events reported in
study participants, but unequal study dropout suggested
that the intervention was not feasible for a heterogeneous
group of women living with advanced breast cancer.
Study participants randomized to the exercise intervention increased their weekly minutes of exercise compared
with controls and experienced increases in physical functioning, but study attrition limited our power to analyze
differences between groups. Given the significant benefits
of exercise in women with early-stage breast cancer, more
work is needed to explore alternative forms of exercise,
potentially in more homogenous groups of women living
with advanced disease, to determine whether exercise
could help women with advanced breast cancer live more
fully with fewer symptoms from their disease and
treatment.
FUNDING SUPPORT
Supported by a grant from the McMackin Foundation.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
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