Order 924380: critically appraised topic and implementation of the evidence

C L I N I C A L T R I A L

Impact of a telephone-based physical activity intervention upon exercise behaviors and fitness in cancer survivors enrolled in a cooperative group setting

Jennifer A. Ligibel • Jeffrey Meyerhardt • John P. Pierce • Julie Najita •

Laura Shockro • Nancy Campbell • Vicky A. Newman • Leslie Barbier •

Eileen Hacker • Marie Wood • James Marshall • Electra Paskett •

Charles Shapiro

Received: 5 October 2011 / Accepted: 10 November 2011 / Published online: 24 November 2011

� Springer Science+Business Media, LLC. 2011

Abstract Observational studies demonstrate an associa-

tion between physical activity and improved outcomes in

breast and colon cancer survivors. To test these observa-

tions with a large, randomized clinical trial, an intervention

that significantly impacts physical activity in these patients

is needed. The Active After Cancer Trial (AACT) was a

multicenter pilot study evaluating the feasibility of a tele-

phone-based exercise intervention in a cooperative group

setting. Sedentary (engaging in \60 min of recreational activity/week) breast and colorectal cancer survivors were

randomized to a telephone-based exercise intervention or

usual care control group. The intervention was delivered

through the University of California at San Diego; partic-

ipants received ten phone calls over the course of the

16-week intervention. All participants underwent assess-

ment of physical activity, fitness, physical functioning,

fatigue and exercise self-efficacy at baseline and after the

16-week intervention. One hundred and twenty-one

patients were enrolled through ten Cancer and Leukemia

Group B (CALGB) institutions; 100 patients had breast

cancer and 21 had colorectal cancer. Participants random-

ized to the exercise group increased physical activity by

more than 100 versus 22% in controls (54.5 vs. 14.6 min,

P = 0.13), and experienced significant increases in fitness

(increased 6-min walk test distance by 186.9 vs. 81.9 feet,

P = 0.006) and physical functioning (7.1 vs. 2.6, P =

0.04) as compared to the control group. Breast and colo-

rectal cancer survivors enrolled in a multicenter, telephone-

based physical activity intervention increased physical

activity and experienced significant improvements in fit-

ness and physical functioning. Lifestyle intervention

research is feasible in a cooperative group setting.

Keywords Breast cancer � Exercise � Cooperative group � Intervention � Physical functioning

Introduction

Studies suggest that lifestyle factors such as physical

activity and functional status are associated with cancer

outcomes. The Nurses’ Health Study investigators dem-

onstrated that women with early-stage breast cancer who

engaged in more than 9 MET-hours/week of physical

activity, equivalent to walking at an average pace for 3 h/

week, had a 50% lower risk of breast cancer recurrence,

breast cancer death and all cause mortality than women

who were inactive [1]. Subsequent to this report, several

additional large prospective cohort studies, encompassing

more than 15,000 patients with early-stage breast cancer,

have demonstrated that women who are physically active

J. A. Ligibel (&) � J. Meyerhardt � J. Najita � L. Shockro � N. Campbell

Dana-Farber Cancer Institute, 450 Brookline Ave Boston,

Boston, MA 02215, USA

e-mail: [email protected]

J. P. Pierce � V. A. Newman � L. Barbier Moores University of California at San Diego Cancer Center,

San Diego, CA, USA

E. Hacker

University of Illinois at Chicago, Chicago, IL, USA

M. Wood

University of Vermont, Burlington, VT, USA

J. Marshall

Roswell Park Cancer Institute, Buffalo, NY, USA

E. Paskett � C. Shapiro James Comprehensive Cancer Center at the Ohio State

University, Columbus, OH, USA

123

Breast Cancer Res Treat (2012) 132:205–213

DOI 10.1007/s10549-011-1882-7

after cancer diagnosis have a 30–50% lower risk of dis-

ease-specific and overall mortality as compared to seden-

tary patients [1–5]. Similar findings have also been

reported for individuals diagnosed with colon cancer [6–8].

Additionally, poor physical functioning, linked to seden-

tary physical activity patterns [9], has long been shown to

be associated with worse survival in patients with advanced

disease [10, 11], and recent work demonstrates a link

between poor physical functioning and decreased overall

and disease-specific survival in patients diagnosed with

early-stage cancers of the breast, head and neck, colon, and

lung [12–15].

These findings have not yet been confirmed in ran-

domized trials. Many small, mostly single-institution,

studies have demonstrated that physical activity interven-

tions are safe in breast cancer patients, and that participa-

tion in an exercise intervention leads to improvements in

physical functioning, fitness, quality of life, and other end

points [16, 17]. However, there have been no randomized

trials looking at the impact of physical activity on disease

outcomes, and the single-institution trials performed to date

do not provide an adequate foundation for the design of a

large-scale trial.

The Active After Cancer Trial (NCT00548236) was

designed to evaluate the feasibility of conducting a tele-

phone-based exercise intervention study in a cooperative

group setting. The study’s primary endpoint was change in

minutes of weekly physical activity. Secondary outcomes

included change in physical functioning, fitness, anthro-

pometric measures, and quality of life.

Methods

Study population

Participants were recruited from medical oncology clinics

at ten Cancer and Leukemia Group B (CALGB) institu-

tions, including both academic institutions and community

practices, between November 2007 and November 2009.

Eligibility criteria included histological evidence of

stage I–III invasive breast, colon or rectal cancer; com-

pletion of all surgery, chemotherapy, and/or radiation

therapy between 2 and 36 months prior to enrollment

(adjuvant hormonal therapy and trastuzumab were

allowed); BMI B 47 kg/m 2 ; and baseline participation in

B60 min of physical activity per week. Baseline exercise

was assessed via the Leisure Score Index (LSI) of the

Godin Leisure-Time Exercise Questionnaire (modified to

include activity duration). Patients were excluded if they

had evidence of persistent or recurrent cancer, other

malignancy, uncontrolled heart disease or other contrain-

dications to exercise.

Medical clearance was obtained from potential partici-

pants’ medical oncologists or primary care providers. The

study was approved by the Institutional Review Board at

the Dana-Farber Cancer Institute and at each of the par-

ticipating sites. Informed consent was obtained from all

participants prior to enrollment.

Study design

After enrollment, participants were randomized 1:1 to an

exercise intervention group or usual care control group.

The intervention group participated in a 16-week tele-

phone-based exercise intervention. The control group

received routine care for 16 weeks and was then offered a

telephone consultation with an exercise trainer at the end of

the control period. Subjects were stratified by type of

malignancy (breast vs. colon/rectal) and gender at the time

of study entry. Assessment of weekly minutes of physical

activity, fitness, anthropometric measures, quality of life,

physical functioning, and fatigue was performed at baseline

and after the completion of the 16-week study period.

Assessment of physical activity was conducted centrally,

and all other study measures were collected at the partic-

ipating sites. Changes in these measures over time were

compared between participants randomized to the exercise

and control groups.

Exercise intervention

Social cognitive theory and client-centered counseling

techniques [18] were used in a telephone-based interven-

tion to motivate participants to increase physical activity.

The intervention consisted of 10–11 semi-structured phone

calls over the 16-week intervention period. Calls were

delivered by behavioral counselors from a Shared Resource

at the Moores UC San Diego Cancer Center. Call duration

was 30–45 min; calls were more frequent during the early

period of the change attempt and became less frequent over

time [19]. Initial calls focused on goal setting and perfor-

mance assessment so as to build self-efficacy for exercise

behaviors, while later calls concentrated upon the adequacy

of plans for relapse prevention. Each call reviewed per-

formance on the behaviors previously discussed and

encouraged the participant to keep using self-regulatory

skills to achieve change. The telephone calls were sup-

plemented by a Participant Workbook, which included

additional information regarding the importance of exer-

cise in cancer populations, guidelines for exercise safety,

and journal pages to track weekly exercise.

The weekly exercise target was performance of at least

180 min of moderate-intensity physical activity, based on

the results of observational studies demonstrating better

survival in patients with early-stage breast and colorectal

206 Breast Cancer Res Treat (2012) 132:205–213

123

cancer who engaged in 3–5 h of moderate activity per

week [1–3, 6, 7]. Participants were allowed to choose their

own form of exercise, as long as it involved moderate to

strenuous activity (as defined in Ainsworth’s Compendium

of Physical Activities [20]). Participants were provided

with a pedometer (New Lifestyle Digi-Walker) and asked

to wear this daily. Instructions for using the pedometer

were included in the Participant Workbook and were

reviewed during the first counseling session. Participants

were asked to record the number of minutes of exercise

they performed and steps they completed each day in

journals, which were reviewed during the telephone

counseling calls.

Quality assurance

The UCSD Cancer Prevention Program counselors com-

plete an intensive 80-h program providing training in

conducting physical activity and dietary assessments, the

principles and practice of client-centered counseling, and

use of computer-based structured counseling protocols.

Counselors practice extensive role-playing before con-

ducting their first counseling session. To ensure the fidelity

of the intervention, the counselors used a computer-assisted

program that provided them with scripted questions that

required them to enter respondent answers at each point.

These scripted calls were contained within a detailed

relational database that provided the call schedule, range

checks on keyed responses, and management reports.

Measurements

Demographic data and disease and treatment information

were collected at the time of participant enrollment. The

study’s primary outcome was change in minutes of weekly

physical activity over the course of the 16-week study

period. Physical activity was measured with the 7-Day

Physical Activity Recall (7-Day PAR) Interview, an

instrument that provides information regarding the duration

and intensity of physical activity performed. The 7-Day

PAR has been widely used to quantify physical activity

levels in a variety of epidemiologic and interventional

studies [21–23] and has been demonstrated to correlate

with changes in VO2 max, body composition [21, 24, 25],

and activity patterns generated through direct observation

or activity monitors [25, 26]. 7-Day PAR interviews were

conducted over the telephone by a blinded member of the

study staff at the Dana-Farber Cancer Institute. Weekly

minutes of physical activity and weekly metabolic task

equivalent-hours (MET-hours) of activity were recorded at

baseline and at week 16 for all study participants.

Participants also underwent a series of anthropometric,

fitness, and quality of life measurements at both time points.

Measurements were conducted by study staff at participating

institutions. Body weight and height were measured with

participants wearing street clothes and no shoes. These data

were used to calculate Body Mass Index (BMI) using the

formula BMI = weight (kg)/height (m) 2 . Waist circumfer-

ence was measured at the bending line, and hip measurement

was recorded at the point of maximum girth.

Fitness was assessed through the 6-Minute Walk Test

(6MWT), an objective evaluation of functional exercise

capacity that has been shown to be highly correlated with

the 12 Minute Walk Test [27] (from which it was derived)

and with cycle ergometer and treadmill based exercise tests

[28]. The 6MWT measures the distance an individual

walks on a level, indoor surface in 6 min. Given space

limitations, each participating site was provided with a stop

watch and 100 foot tape measure. Investigators identified a

stretch of hallway at least 50 feet in length, and participants

walked back and forth along the tape measure for 6 min.

Quality of life (QOL) and physical functioning were

assessed with the European Organization for Research and

Training, Quality of Life Questionnaire—Core 30, Version

3.0 (EORTC QLQ-C30). The EORTC QLQ-C30 is a well-

established instrument in cancer clinical trials, and the

psychometric properties have been previously reported [29,

30]. This 30-item instrument consists of five functional

scales (including physical functioning), a global QOL/

health status scale, three multi-item symptom scales, and a

number of single-item questions. Items on the multi-item

subscales are averaged and then converted to a scale with a

range of 0 to 100. Higher scores on the five functional

scales and the global QOL/health status scale represent a

higher level of functioning. Higher scores on the symptom

scales and the single-item questions indicate a higher

degree of symptomatology, and thus a poorer QOL.

Fatigue was assessed with the FACIT Fatigue Scale, a

validated 13-item scale designed to assess fatigue in terms of

its intensity and interference with performing everyday

functions [31, 32]. Exercise readiness was assessed with the

Physical Activity Self-Efficacy Questionnaire developed by

Marcus et al. [33], a five-item scale that rates participants’

confidence regarding their ability to be physically active in

various situations.

Statistical analysis

The study’s primary endpoint was change in minutes of

self-reported physical activity, as measured by the 7-Day

PAR. With a sample size of 120 patients, we had more than

80% power to detect a difference of 75 min of activity per

week (change in minutes per week of 165 vs. 90) between

the arms using a 2-sided 0.05 level Wilcoxon rank-sum

test. This was based on the following assumptions: both

groups would engage in 60 min of moderate-vigorous

Breast Cancer Res Treat (2012) 132:205–213 207

123

activity per week at baseline, the control group would

increase activity to 90 min/week over the study period

given a potential increase in activity after the completion of

adjuvant therapy, a standard deviation (SD) of 120 min/

week [34] and a drop out rate of 20% [35, 36].

Analyses for the changes in minutes of weekly activity,

fitness, anthropometric measurements and QOL outcomes

included participants for whom both baseline and week 16

measurements were available. Change scores were not

imputed for patients who had data missing at either time

point and these patients were excluded from the analysis

(n = 22). The arms were compared using a Wilcoxon rank-

sum test or two-sample t tests, after inspection of histo-

grams to assess distributional assumptions, accounting for

unequal variances with Satterthwaite’s method. Pearson

correlation coefficients were used to describe the relation-

ship between change in weekly activity and measures of

physical function, pain, fatigue, and QOL.

Descriptive statistics were used to summarize minutes of

weekly activity and number of daily steps recorded in

weekly exercise journals by women randomized to the

exercise intervention. For each participant with at least

8 weeks of recorded data, an average number of minutes of

weekly physical activity and an average number of steps

were calculated. These values were then averaged across

all evaluable participants, resulting in an average number

of minutes of exercise and an average number of steps

performed per week.

Analyses for the changes in minutes of weekly activity,

fitness, anthropometric measurements and QOL outcomes

were repeated with data from the breast cancer cohort only.

As these data were similar to the data from the combined

cohort, all analyses reported included all evaluable study

participants.

Results

One hundred and twenty-one participants enrolled in the

protocol, 100 patients with breast cancer and 21 patients

with colorectal cancer (see Consort Diagram in Fig. 1).

Baseline data are available for 121 participants. Baseline

Assessed for eligibility (n=237) Excluded (n=116)

Not meeting inclusion criteria (n= 72)

Refused to participate (n=40)

Other reasons (n=4; out of state)

Analyzed (n=51)

Excluded from analysis (n= 0)

Lost to follow-up (n= 5)

Give reasons: Did not return study staff’s phone calls (5)

Discontinued participation (n=4)

Give reasons: withdrew upon assignment to control group (1); withdrew consent (2); disease recurrence (1)

Allocated to control (n= 60)

Participated in control (n=51) Did not participate in control (n=9)

Lost to follow-up (n=6)

Give reasons: Did not return study staff’s phone calls (6)

Discontinued intervention (n= 7)

Give reasons: withdrew consent (4), disease recurrence (2), removed due to medical reason (1)

Allocated to intervention (n=61)

Received allocated intervention (n=48)

Did not receive allocated intervention (n=13)

Analyzed (n=48)

Excluded from analysis (n= 0)

Allocation

Analysis

Follow-Up

Enrollment: 121

Randomization

Fig. 1 Consort Diagram

208 Breast Cancer Res Treat (2012) 132:205–213

123

characteristics were distributed similarly in the exercise

and control groups (Table 1). The majority of the partici-

pants were women, had breast cancer and were treated with

chemotherapy, surgery, radiation, and hormonal therapy.

Mean age was 54 and mean BMI 30.9 kg/m 2 . Twenty-two

patients withdrew consent and/or did not complete the

study (Fig. 1). There were no significant differences in

demographic, disease or treatment variables between

patients who completed the protocol and those who drop-

ped out (data not shown).

Exercise intervention

Sixty-one participants were randomized to the exercise

intervention. Although 13 participants ultimately did not

complete the intervention, at least partial exercise data were

available for all participants. Participants attended a median

of nine calls (range 0–11). For patients who completed the

16-week intervention, the range of calls delivered was 7–11.

Forty-one of the 61 participants randomized to the exercise

intervention completed at least 8 weekly exercise journals

during the 16-week intervention period. Compliance with

pedometer use was good, with 30 of the 61 participants

randomized to the intervention group reporting daily steps

for greater than 90% of days during the 16-week interven-

tion periods, and an additional nine patients reporting data

for more than 50% of days. Participants reported a mean of

153.6 (SD 74.6) min of moderate or strenuous exercise per

week and a mean of 7392 (SD 1619) steps per day.

Physical activity, physical functioning, and fitness

Physical activity behaviors were assessed in all study

participants with the 7-Day Physical Activity Recall

Interview, physical functioning was assessed with the

EORTC QLQ C30, and fitness was assessed with the

6-Minute Walk Test. Baseline and week-16 physical

activity and physical functioning data were available for 99

patients; fitness data at both time points were available for

97 patients. At baseline, both groups were relatively inac-

tive (Table 2); control participants reported a median of

65.7 min of moderate or strenuous exercise per week on

the 7-Day PAR and intervention participants 44.9 min

(P = 0.12). Over the 16-week study period, the interven-

tion group increased activity by 121% or 54.5 (±142.0)

min versus 22% or 14.6 (±117.0) min in control patients

(P = 0.13). MET-hours/week also increased by a non-

significant amount in intervention participants versus con-

trols (3.0 ± 8.2 vs. 1.0 ± 7.6, P = 0.23).

Participants randomized to the intervention group sig-

nificantly increased fitness and physical functioning over

the course of the 16-week study period compared to con-

trols (Table 2). Intervention participants increased the

distance they walked over 6 min by 186.9 (±215.1) feet

versus 81.9 (±135.2) feet in control participants (P =

0.006). Intervention participants also experienced a sig-

nificant improvement in self-reported physical functioning

Table 1 Baseline and treatment characteristics

Exercise

(N = 61) Control

(N = 60)

Age (±SD) 53.1 (10.8) 55.5 (10.6)

BMI (kg/m 2 ) 31.2 (6.2) 30.6 (5.3)

Cancer type

Breast 50 (82%) 50 (83%)

Colon 9 (15%) 8 (13%)

Rectal 2 (3%) 2 (3%)

Sex

Female 56 (92%) 56 (93%)

Male 5 (8%) 4 (7%)

Race

White 56 (92%) 55 (92%)

Black 4 (7%) 5 (8%)

Asian 1 (2%) 0 (0%)

Highest level of education

Some/no high school 1 (2%) 3 (5%)

High school graduate 11 (18%) 6 (10%)

Technology school/some college 16 (26%) 20 (33%)

College graduate/advanced degree 33 (54%) 31 (52%)

Employment status

Working full time 22 (36%) 25 (42%)

Working part time 11 (18%) 11 (18%)

Homemaker 6 (10%) 4 (7%)

Retired 7 (11%) 13 (22%)

Disabled 3 (5%) 3 (5%)

Unemployed 4 (7%) 2 (3%)

Other 8 (13%) 2 (3%)

Tumor stage

Stage I 20 (33%) 21 (35%)

Stage II 19 (31%) 23 (38%)

Stage III 22 (16%) 16 (27%)

Surgery for primary tumor

Breast (n = 100)

Mastectomy 25 (50%) 26 (52%)

Lumpectomy 25 (50%) 24 (48%)

Colon (n = 21)

Partial colectomy 4 (36%) 7 (70%)

Low anterior resection 5 (45%) 0 (0%)

Colostomy 2 (18%) 2 (20%)

Chemotherapy 47 (77%) 43 (72%)

Radiation 42 (69%) 33 (55%)

Hormonal therapy (Breast Cancer) 31 (62%) 36 (72%)

Breast Cancer Res Treat (2012) 132:205–213 209

123

as compared to controls (change of 7.1 ± 11.4 points vs.

2.6 ± 10.2 points on the EORTC QLQ C30 physical

functioning subscale, P = 0.04) (Table 2).

Quality of life and fatigue

Participants completed quality of life, fatigue, and exercise

self-efficacy questionnaires at baseline and 16 weeks

(Table 3). At baseline, participants in both groups reported

good overall quality of life, and moderate levels of fatigue

and exercise self-efficacy. Participants in the intervention

group reported trends toward improvement in QOL

(4.3 ± 16.0 vs. -1.5 ± 18.8, P = 0.10) and exercise self-

efficacy (0.1 ± 1.0 vs. -0.3 ± 1.0, P = 0.06) as com-

pared with controls. There were no significant differences

in change scores for fatigue or other QOL subscales

between groups.

Physical measurements

Baseline and week-16 anthropometric data were available

for 99 participants (Table 4). At baseline, participants on

average weighed about 83 kg and had a BMI slightly less

than 31 kg/m 2 . There were no significant changes in

anthropometric measures over the course of the study in

either group.

Discussion

Our study tested the ability of a telephone-based physical

activity intervention to increase weekly physical activity

and improve physical functioning and fitness in 121 sed-

entary breast and colorectal survivors recruited from ten

CALGB institutions. The intervention led to statistically

significant and clinically meaningful improvements in

Table 2 Physical activity behaviors, fitness, and physical functioning at baseline and change over 16 weeks

Baseline Change over 16 weeks

Exercise (n = 48) Control (n = 51) P Exercise (n = 48) Control (n = 51) P

Physical activity (min/week) a

44.9 ± 58.5 65.7 ± 84.1 0.12 54.5 ± 142.0 14.6 ± 117.2 0.13

MET-hours/week b

2.7 ± 3.6 4.0 ± 5.0 0.10 3.0 ± 8.2 1.0 ± 7.6 0.23

6-Minute Walk Test (feet) 1431.9 ± 309.1 1495.2 ± 246.3 0.22 186.9 ± 215.1 81.9 ± 135.2 0.006

Physical functioning (EORTC QLQ C-30) 82.8 ± 17.8 85.8 ± 11.9 0.29 7.1 ± 11.4 2.6 ± 10.2 0.04

All data are presented as means ± SD a

As measured by the 7-Day Physical Activity Recall

Table 3 Baseline and change data for quality of life, fatigue, and related outcomes

Baseline Change over 16 weeks

Exercise (n = 48) Control (n = 51) P Exercise (n = 48) Control (n = 51) P

EORTC QLQ C-30

Global QOL 67.1 ± 20.2 71.8 ± 18.3 0.18 4.3 ± 16.0 -1.5 ± 18.8 0.10

Pain 19.7 ± 24.6 21.9 ± 24.1 0.61 -4.9 ± 17.5 -2.6 ± 27.4 0.63

Insomnia 32.8 ± 29.5 35.0 ± 29.7 0.68 -2.1 ± 30.3 -8.5 ± 29.7 0.29

FACIT fatigue scale 36.9 ± 10.9 38.6 ± 8.5 0.34 4.4 ± 8.4 2.5 ± 6.8 0.23

Exercise self-efficacy scale 2.8 ± 1.0 2.9 ± 1.0 0.32 0.1 ± 1.2 -0.3 ± 0.8 0.06

Data are presented as means (SD)

Table 4 Physical measurements at baseline and change over 16 weeks

Baseline Change over 16 weeks

Exercise (n = 48) Control (n = 51) P Exercise (n = 48) Control (n = 51) P

Weight (kg) 83.5 ± 18.1 82.8 ± 16.0 0.82 -0.3 ± 2.9 -0.4 ± 3.1 0.85

Waist circumference (cm) 96.7 ± 20.0 94.0 ± 16.1 0.41 1.4 ± 13.2 2.3 ± 9.4 0.70

Hip circumference (cm) 110.1 ± 19.8 112.9 ± 18.5 0.41 2.4 ± 14.6 0.8 ± 11.3 0.53

Data are presented as means (SD)

210 Breast Cancer Res Treat (2012) 132:205–213

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fitness and functional status. At baseline, both groups

walked approximately 1,450 feet over the course of 6 min,

somewhat lower than the average of 1,820 feet for women

and 1,919 feet for men reported in trials of healthy adults

[37]. Intervention participants increased their distance on

the 6-Minute Walk Test by 186.9 feet (compared to 81.9

feet in controls, P = 0.006), a change that has been cor-

related with significant improvements in functional status

in other studies [38, 39]. Self-reported physical functioning

also improved by 7.1 points in the intervention group (vs.

2.6 in controls, P = 0.04), consistent with a clinically

meaningful improvement in functional status [40, 41].

Finally, physical activity increased by 54 min/week in the

intervention group compared to 14 min/week in the control

group (P = 0.13).

The increase in weekly minutes of physical activity seen

in our study is generally consistent with other multicenter,

distance-based lifestyle interventions. In RENEW [42],

older (age C65) survivors of breast, prostate, and colorectal

cancer randomized to a telephone-based diet and exercise

intervention increased exercise by an average of 31 min/

week more than survivors randomized to an education

control group (P \ 0.001). In FRESH START [34], patients with breast or prostate cancer randomized to a

mail-based diet and exercise intervention increased weekly

physical activity by 59.3 versus 39.2 min in the education

control group (P = 0.02). Finally, in ACTION [43] breast

cancer survivors provided with pedometers, with or with-

out tailored print materials about exercise, significantly

increased self-reported physical activity versus controls

(increase of 30 min/week controls, 89 min/week pedome-

ters, and 87 min pedometer ? printed materials, P =

0.017 and P = 0.022, respectively). However, there were

no increases in daily steps in any of the four groups.

Despite the modest increase in weekly physical activity

seen in our study, intervention participants experienced

significant improvements in fitness and physical function-

ing. Emerging data suggest that physical functioning and

physical health may be related to cancer outcomes in

patients with early-stage disease. A meta-analysis of 30

trials looking at survival and health-related quality of life

showed that physical functioning was significantly related

to survival in analyses adjusted for disease stage (HR 0.94,

95% CI 0.92–0.96, P \ 0.001) [13]. Gupta et al. [12] also demonstrated that women with newly diagnosed breast

cancer who had higher physical functioning scores had a

mean survival of 35.5 versus 17.8 months in patients with

lower scores (P = 0.0006). These findings could explain,

at least in part, the improved survival seen in patients who

engage in even modest levels of physical activity after

cancer diagnosis. As seen in our study and others [42],

even small increases in physical activity can lead to

significant improvements in physical functioning and

fitness.

Our study also demonstrated the feasibility of conducting

lifestyle research in a cooperative group setting. Enrollment

of 121 patients was completed over 2 years, and our attri-

tion rate of 18% is similar to other exercise intervention

studies targeting inactive cancer survivors, including those

involving in-person exercise interventions [35, 36]. Partic-

ipants received a median of 9 out of a planned 10–11 calls

during the intervention period. The data completion rate was

[98% for the 99 patients who finished the study, and sites were uniformly successful in collecting study measures,

including the 6-Minute Walk test, a novel measure for the

majority of the participating sites. This type of distance-

based lifestyle intervention could be utilized in a large-scale

cooperative group study to test the impact of behavior

change upon breast cancer outcomes.

A number of weaknesses of our study should be

acknowledged. First, the trial was powered to detect a

75-min difference in the increase in minutes of weekly

activity between the exercise and control groups. Given

that the between-group difference was only 40 min and

that the standard deviations were large, we did not dem-

onstrate that our intervention significantly increased phys-

ical activity. Although the improvements in fitness and

functional measures suggest that the exercise group did

increase activity, a larger sample would have been required

to determine the statistical significance of a 40-min dif-

ference in minutes of exercise between the groups. Addi-

tionally, our study was initially intended to enroll equal

proportions of breast and colorectal survivors, with a plan

to conduct separate analyses of our end points in both

groups. Given the slower than anticipated enrollment in the

colorectal cancer group, the majority of our participants

were breast cancer survivors. We were thus not able to

conduct a separate analysis in the colorectal cancer sub-

group, and it is not clear how applicable the results of this

study are for colorectal cancer survivors.

In conclusion, this trial demonstrates the ability of a

telephone-based exercise intervention to improve fitness

and physical functioning in breast cancer survivors, as well

as the feasibility of conducting a lifestyle intervention in a

cooperative group setting. Sites without experience in

conducting lifestyle research were able to recruit patients

and collect study measures, including an objective fitness

measure. The lifestyle intervention led to a non-significant

increase in weekly minutes of physical activity, but par-

ticipants significantly improved functional measures linked

to survival in observational studies. Further work is needed

to determine the most effective lifestyle interventions, and

to test the impact of lifestyle change upon outcomes in

cancer survivors.

Breast Cancer Res Treat (2012) 132:205–213 211

123

Acknowledgments This work was supported by a Cancer and Leukemia Group B Pilot Prevention Grant and by the Gloria Spivak

Faculty Support Fund at the Dana-Farber Cancer Institute.

Conflict of interest None.

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