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Exercise for women receiving adjuvant therapy for breast
cancer (Review)
Markes M, Brockow T, Resch KL
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2009, Issue 1
http://www.thecochranelibrary.com
Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
27DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Exercise versus control, Outcome 1 Cardiorespiratory fitness. . . . . . . . . . . 27
Analysis 1.2. Comparison 1 Exercise versus control, Outcome 2 Strength. . . . . . . . . . . . . . . . 28
Analysis 1.3. Comparison 1 Exercise versus control, Outcome 3 Fatigue. . . . . . . . . . . . . . . . . 28
Analysis 1.4. Comparison 1 Exercise versus control, Outcome 4 Weight change. . . . . . . . . . . . . . 29
Analysis 1.5. Comparison 1 Exercise versus control, Outcome 5 Cancer specific quality of life. . . . . . . . . 29
Analysis 1.6. Comparison 1 Exercise versus control, Outcome 6 Cancer site-specific quality of life. . . . . . . . 30
Analysis 1.7. Comparison 1 Exercise versus control, Outcome 7 Anxiety. . . . . . . . . . . . . . . . . 30
Analysis 1.8. Comparison 1 Exercise versus control, Outcome 8 Mood disturbance. . . . . . . . . . . . . 31
Analysis 1.9. Comparison 1 Exercise versus control, Outcome 9 Depression. . . . . . . . . . . . . . . 31
Analysis 1.10. Comparison 1 Exercise versus control, Outcome 10 Natural killer cells. . . . . . . . . . . . 32
Analysis 1.11. Comparison 1 Exercise versus control, Outcome 11 T-cells. . . . . . . . . . . . . . . . 32
Analysis 1.12. Comparison 1 Exercise versus control, Outcome 12 Oxidative stress. . . . . . . . . . . . . 33
Analysis 1.13. Comparison 1 Exercise versus control, Outcome 13 Nausea relief. . . . . . . . . . . . . . 33
Analysis 1.14. Comparison 1 Exercise versus control, Outcome 14 Sleep disturbances. . . . . . . . . . . . 34
34ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
36APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
39INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iExercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Exercise for women receiving adjuvant therapy for breastcancer
Martina Markes1, Thomas Brockow2 , Karl-Ludwig Resch3
1Rehabilitation Research Institute, FBK German Institute for Health Research, Bad Elster, Germany. 2Physical medicine and reha-
bilitation, Rehabilitation Research Institute, Bad Elster, Germany. 3Physical Medicine and Rehabilitation, FBK German Institute for
Health Research, Bad Elster, Germany
Contact address: Martina Markes, Rehabilitation Research Institute, FBK German Institute for Health Research, Lindenstr. 5, Bad
Elster, 08645, Germany. martina.markes@d-i-g.org.
Editorial group: Cochrane Breast Cancer Group.
Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 15 July 2004.
Citation: Markes M, Brockow T, Resch KL. Exercise for women receiving adjuvant therapy for breast cancer. Cochrane Database ofSystematic Reviews 2006, Issue 4. Art. No.: CD005001. DOI: 10.1002/14651858.CD005001.pub2.
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence
and mortality rates. On the other hand, adjuvant therapy with agents such as hormone therapy, chemotherapy and radiotherapy impacts
on quality of life due to substantial short- and long-term side effects.
Objectives
To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side
effects such as physical deterioration, fatigue, psychosocial distress and physiological, morphological and biological changes.
Search methods
We searched the Cochrane Breast Cancer Specialised Register (16 July 2004) and the following electronic databases: MEDLINE (1966
to 2004), EMBASE (1988 to 2004), CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE
(1880 to 2004), ProQuest Digital Dissertations (1861 to 2004) and Conference Papers Index (1973 to 2004). Furthermore, we screened
references in relevant reviews and clinical trials and handsearched relevant journals.
Selection criteria
We included randomised and non-randomised controlled trials that examined aerobic or resistance exercise, or both, in women
undergoing adjuvant treatment for breast cancer.
Data collection and analysis
Two authors independently extracted data and assessed methodological quality and adequacy of the training stimulus following a set
of standardised criteria. Meta-analyses were performed for physical fitness, fatigue and weight gain using a random-effects model.
1Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Main results
Nine trials involving 452 women met the inclusion criteria. Meta-analysis for cardiorespiratory fitness (involving 207 participants)
suggested that exercise improves cardiorespiratory fitness (SMD 0.66, 95% CI 0.20 to 1.12). Meta-analysis for fatigue (317 partici-
pants) found statistically non-significant improvements for participants in the exercise intervention groups compared to control (non-
exercising) groups (SMD -0.12, 95% CI -0.37 to 0.13); the same applied for the meta-analysis of weight gain (147 participants) (SMD
-1.11, 95% CI -2.44 to 0.22). Evidence for other outcomes remains limited. Adverse effects (lymphedema and shoulder tendonitis)
were observed in two trials. The results from non-randomised controlled trials are similar to those of randomised controlled trials and
do not appear to produce any bias. This review is based on a small number of trials with a considerable degree of clinical heterogeneity
regarding adjuvant cancer treatments and exercise interventions.
Authors’ conclusions
Exercise during adjuvant treatment for breast cancer can be regarded as a supportive self-care intervention which results in improved
physical fitness and thus the capacity for performing activities of daily life, which may otherwise be impaired due to inactivity during
treatment. Improvements in fatigue were ambiguous and there was a lack of evidence for improvement with exercise for other treatment-
related side effects. Since exercise interventions (for sedentary participants) require behaviour change, strategies for behaviour change
should underpin these interventions. Furthermore, long-term evaluation is required due to possible long-term side effects.
P L A I N L A N G U A G E S U M M A R Y
Exercise for women receiving adjuvant therapy for breast cancer
In the past, cancer patients were usually advised to rest and avoid physical effort. However, it is now well established that excessive
rest and lack of physical activity may result in severe deconditioning and thus reduced physical functioning. Furthermore, women
undergoing chemotherapy or radiation therapy as adjuvant treatment for breast cancer commonly experience debilitating side effects.
One of the main side effects of radiation therapy is fatigue; common side effects of chemotherapy are nausea and vomiting, fatigue,
weight gain and mood disturbances. These side effects interfere with daily activities such as self-care or return to work. Physical exercise
has been reported to improve the underlying conditions in people with a range of chronic diseases.
This review evaluated physical exercise as a means of counteracting several of the side effects that cancer treatments (chemotherapy
and radiation therapy) induce. It included nine controlled clinical trials with a total of 452 participants. Results suggest that physical
exercise can improve physical function even during cancer treatment. Also, fatigue may be lessened through exercise although there
is insufficient evidence to conclude this. There is still not enough evidence about the effect of exercise on outcomes such as mood
disturbances, immune function and weight gain. Moreover, there is a lack of evidence for harms of exercise during adjuvant cancer
treatment.
B A C K G R O U N D
Breast cancer detection and management have undergone dra-
matic changes over the past three decades. Women are increasingly
diagnosed with early-stage disease leaving them with treatment
choices ranging from breast conserving options to mastectomy
(Newman 2003). With the majority of breast cancers diagnosed at
an early stage, treatment is focused on cure and the prevention of
relapse due to micrometastatic disease. Because systemic adjuvant
therapy effectively prevents or delays some relapses and deaths in
early-stage disease, this treatment approach has become standard
practice throughout most of the Western world (Hudis 2003).
The mainstay of care is local therapy, consisting of surgery (with
or without radiotherapy), along with systemic adjuvant therapy,
which includes chemotherapy (cytotoxic agents), hormonal ther-
apy or a combination of these treatments.
Besides these major advances in managing both early and locally
advanced breast cancer, patients still have to deal with severe side
effects and psychological distress during adjuvant therapy. This has
a substantial impact on their quality of life. Side effects that appear
with adjuvant cancer treatment differ depending on the mode
of treatment, that is, radiotherapy, chemotherapy or hormonal
2Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
therapy.
Radiotherapy is associated with short-term side effects such as fa-
tigue and skin erythema and long-term side effects including lym-
phedema, cardiac and pulmonary toxicities and brachial plexopa-
thy (Truong 2004). Chemotherapy is associated with short-term
side effects such as emesis, nausea, stomatitis, alopecia, myelosup-
pression, thromboembolism, myalgias, neuropathy and fatigue.
Long-term side effects of chemotherapy are premature menopause,
weight gain, fatigue, cardiac dysfunction and cognitive dysfunc-
tion (Partridge 2001). Furthermore, patients receiving radiother-
apy or chemotherapy report anxiety and depression prior to, dur-
ing and after therapy due to treatment side effects (Spiegel 1997).
Adjuvant hormonal therapy produces symptoms secondary to oe-
strogen withdrawal, such as hot flushes, bone demineralisation and
psychosexual effects (Rutqvist 2004).
Although research is producing increasingly hopeful insights into
the causes and cures for cancer, efforts to manage the side effects
of adjuvant therapy have not kept pace (Patrick 2003). Exercise
interventions may be effective in managing some of these side
effects, such as fatigue, weight gain, emotional distress, nausea and
vomiting and premature menopause.
Cancer-related fatigue is defined by the National Comprehensive
Cancer Network as a “persistent, subjective sense of tiredness re-
lated to cancer or cancer treatment that interferes with usual func-
tioning” (NCCN 2004). Fatigue results in substantial physical,
psychosocial, cognitive and socioeconomic consequences (Holley
2000). Acute and chronic radiotherapy-related fatigue occurs in up
to 80% and 30% of patients, respectively (Jereczek-Fossa 2001).
During and after adjuvant chemotherapy the prevalence of fatigue
is high and fluctuating (de Jong 2002), with a frequency of 60%
to 90% (Feyer 2001). Fatigue is also associated with factors such
as depression, impaired quality of sleep or pain (de Jong 2002).
The rationale supporting exercise interventions for cancer-related
fatigue is based on the proposition that the combined effects of a
toxic treatment and a decreased level of activity during treatment
cause a reduction in the capacity for physical performance. Pa-
tients must, therefore, use greater effort and expend more energy
to perform daily activities, which leads to fatigue (NCCN 2004).
Physical exercise training programmes may increase functional ca-
pacity leading to reduced effort and decreased fatigue.
Weight gain is also common among breast cancer patients receiv-
ing adjuvant chemotherapy, with gains ranging from 0 to 22 kg,
influenced by menopausal status, nodal status and the type, dura-
tion and intensity of treatment (Demark-Wahnefried 97). Weight
gain not only has a similar profound effect on quality of life as fa-
tigue but in addition it indicates a potentially poor prognosis, with
higher relapse rates and poorer survival (Camoriano 1990). Evi-
dence suggests that overeating is not a cause of weight gain among
breast cancer patients who receive chemotherapy but is the result
of reduced physical activity. Chemotherapy induced weight gain
shows the distinctive pattern of sarcopenic obesity that is weight
gain in the presence of lean tissue loss or absence of lean tissue gain
(Demark-Wahnefried 01). The development of sarcopenic obesity
with evidence of reduced physical activity supports the need for
interventions focused on exercise, especially resistance training.
Women treated for breast cancer frequently experience higher
levels of emotional distress than the general population (Spiegel
1997). The rationale for considering exercise as an intervention
to reduce distress in women receiving adjuvant therapy for breast
cancer is based upon the literature that has demonstrated amelio-
rating effects of exercise on these problems. Results of studies with
non-cancer populations indicate that aerobic exercise training has
antidepressant and anxiolytic effects and protects against harm-
ful consequences of stress (Salmon 2001). There is evidence that
cognitive dysfunction may also occur in women receiving adju-
vant chemotherapy for breast cancer (O’Shaughnessy 2003; Rugo
2003; Tchen 2003). A meta-analytic study conducted to examine
the hypothesis that aerobic fitness training enhances the cognitive
vitality of healthy but sedentary older adults indicated that fitness
training has robust benefits for cognition (Colcombe 2003).
The incidence and severity of nausea and vomiting in patients re-
ceiving chemotherapy are affected by numerous factors including
the specific chemotherapeutic agents used, their dosage, the sched-
ule and route of administration and individual patient variability.
Although standard chemotherapy regimens for breast cancer are
considered to be mildly to moderately emetogenic (Dibble 2003),
nausea and vomiting do occur with these regimens: 73 to 82% of
women receiving chemotherapy for breast cancer experience nau-
sea (Dibble 2003). If emesis is severe it can in turn lead to antic-
ipatory nausea and vomiting (Morrow 1998). Winningham et al
suggested that aerobic exercise may serve as a potential interven-
tion for controlling or mitigating chemotherapy induced nausea
(Winningham 1988).
Currently, exercise does not appear as an inherent part of cancer
care. Exercise is actually considered an essential component in car-
diopulmonary rehabilitation; however, its role in oncological reha-
bilitation programmes has thus far been mostly limited to physical
treatment addressing specific impairments caused, for example, by
amputation or surgery (Dimeo 2000). Evidence concerning the
natural progression of physical activity suggests that women with
breast cancer significantly decrease physical activity and exercise
from pre-diagnosis to post-diagnosis (Irwin 2003). These decreases
are associated with adjuvant cancer treatment: observed decreases
in physical activity were greater among women who were treated
with radiation and chemotherapy (50% decrease) compared with
women who underwent surgery only (24% decrease) or who were
treated with radiation only (23% decrease) (Irwin 2003).
The role of exercise in breast cancer was examined in retrospective,
cross-sectional and prospective studies (Courneya 2001; Courneya
2002; Courneya 2003; Pinto 1999) with the majority of research
3Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
focused on rehabilitation and health promotion in women who
had completed cancer treatment. This review aims to evaluate
the role of exercise in managing common side effects of adjuvant
therapy for breast cancer.
O B J E C T I V E S
To systematically assess the effectiveness and safety of exercise
training (aerobic or resistance exercise, or both) during adjuvant
treatment for breast cancer in reducing treatment-related side ef-
fects. These include physical deterioration, fatigue, psychosocial
distress and physiological, morphological and biological changes.
M E T H O D S
Criteria for considering studies for this review
Types of studies
We considered randomised and non-randomised controlled trials
of exercise training during adjuvant treatment (radiotherapy, che-
motherapy, hormonal therapy) for women with non-metastatic
breast cancer.
We defined a controlled trial as a trial with at least two groups
where the trial investigator assigned participants to the experimen-
tal or control group using randomisation, a quasi-randomisation
procedure or some other method of allocation. We excluded trials
if group assignment was based on self selection.
Types of participants
We included trials with women who were diagnosed with breast
cancer stages I, II and III and who were undergoing adjuvant (in-
cluding neo-adjuvant) chemotherapy, hormonal therapy or radio-
therapy concurrently with an exercise intervention in the active
group.
Types of interventions
Studies that assessed the effects of all forms of repeatedly per-
formed aerobic or resistance exercise, or both, with programme
duration of at least six weeks were considered for inclusion. To
be included in this review, the exercise intervention had to coin-
cide with the adjuvant treatment regimen rather than follow it.
We excluded studies where the exercise intervention was part of
a complex intervention (for example complete decongestive lym-
phatic therapy). Trials with interventions restricted to local mus-
cular endurance (for example training of shoulders, back or legs
only) instead of including all major muscle groups or restricted to
stretching exercises were also excluded.
We included trials making the following comparisons:
• exercise versus no exercise;
• exercise versus other interventions (e.g. psychosocial
interventions).
Types of outcome measures
Trials that assessed measures related to any of the following out-
comes were considered for inclusion:
• physical fitness (e.g. cardiorespiratory fitness, physical
performance, muscular fitness);
• physiological outcomes;
• multidimensional outcomes (e.g. pain, fatigue, quality of
life);
• psychological distress outcomes;
• biological outcomes (e.g. related to immune function);
• morphological outcomes (e.g. body weight or lean body
mass);
• physical activity behaviour;
• harms.
Search methods for identification of studies
1. Electronic databases
a) The Cochrane Breast Cancer Specialised Register (16 July 2004)
Details of the search strategy applied by the Group to create the
register, and the procedure used to code references, are described
in the Group’s module on The Cochrane Library. We extracted
studies coded as ’exercise’ and ’early’, ’locally advanced’, local re-
currence’ and ’locoregional’ on the Specialised Register for con-
sideration.
b) MEDLINE (1966 to 2006)
The MEDLINE search strategy incorporated the sensitive search
strategy for randomised and controlled trials by Dickersin (
Dickersin 1994), the Cochrane Breast Cancer Group’s strategy for
the identification of populations with ’breast neoplasms’ (Simes
2004) and key words to identify exercise interventions. We mod-
ified this strategy for searching the other databases. In order to
apply the most sensitive approach, we allowed for all breast cancer
survivors instead of limiting our search to breast cancer survivors
currently undergoing cancer treatment. This inclusion criterion
of cancer treatment was accounted for in the process of selecting
studies (see Appendix 1).
c) EMBASE (1988 to 2004)
d) CINAHL (1982 to 2004)
e) SPORTDiscus (1975 to 2004)
f ) PsycINFO (1872 to 2003)
g) SIGLE (1880 to 2004)
h) ProQuest Digital Dissertations (1861 to 2004)
i) Conference Papers Index (1973 to 2004)
4Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
2. References from published studies
We screened references in relevant reviews and in published clinical
trials for further trials.
3. Handsearching
a) Psycho-Oncology (1997 to 2004)
b) Cancer (1990 to 2004)
c) Breast Cancer Research and Treatment (1990 to 2004)
d) Nursing Research (1996 to 2004)
e) Applied Nursing Research (1994, 2000 to 2004)
f ) International Journal of Sports Medicine (1990 to 2004)
g) Medicine & Science in Sports & Medicine (1980 to 2004)
h) Clinical Journal of Sport Medicine (2000 to 2004)
i) Deutsche Zeitschrift für Sportmedizin(1985 to 2004)
j) Oncology Nursing Forum (2000 to 2004)
k) The Physician and Sportsmedicine (1990 to 2003)
l) European Journal of Sport Science (2000 to 2004)
4. Other
We consulted 31 experts in the field of cancer and exercise to
identify additional trials. No language restrictions were applied.
Data collection and analysis
Selection of trials
Initially, two review authors (TB, MM) independently selected
reports potentially fulfilling the inclusion criteria of this review
based on title and abstract. Full articles of any possibly relevant
reports were retrieved for more detailed evaluation. Both authors
then independently performed a final selection of trials to be in-
cluded in the review using a standardised form (eligibility form
plus instruction sheet for assessing eligibility) that was designed
for this review. The decision algorithm required the fulfillment of
our predefined eligibility criteria (see Table 1). A report was ex-
cluded according to the first criterion that it did not fulfill. Dis-
agreements were resolved by consensus; if necessary a third person
was consulted to reach a final decision.
Data extraction
Two review authors (TB, MM) independently extracted data (in-
cluding study characteristics, study results and point estimates to-
gether with measures of variability for selected outcome variables)
using a data extraction form together with coding instructions
for data collection, both designed for this review. Where further
or missing data were required, authors of studies were contacted.
All discrepancies were reviewed and consensus achieved by discus-
sion.
Methodological quality assessment
Methodological quality was assessed independently by two review
authors (TB, MM) each applying a study quality form as well as a
code of practice for implementing quality criteria, both designed
for this review. Disagreement was resolved by consensus and, if dis-
agreement persisted, a third review author (KLR) was consulted for
a final decision. We applied the van Tulder methodological quality
criteria (van Tulder 1997) with all criteria carrying equal weight,
but we customised these criteria with two deviations regarding
blinding requirements: we regarded blinding of care providers and
participants as not applicable to exercise interventions and thus
omitted these items (see Table 2). However, blinding of outcome
assessment was included as a quality criterion. Each criterion was
answered with ’yes’, ’no’ or ’n/a’ (not available); answers were coded
with: ’yes’ as ’+’, ’no’ as ’-’ and ’n/a’ as ’?’. A quality score was cal-
culated for each study by summing positive scores for individual
items, resulting in a possible score from 0 to 17. Moderate quality
was defined as fulfilling a score between 9 and 12 (50 to 74%)
of all methodological quality criteria; high quality was defined as
fulfilling at least 13 (> 75%) of all methodological quality criteria.
Analysis of training stimulus
Analysis of the training stimulus roughly followed the American
College of Sports Medicine (ACSM) guidelines for exercise pre-
scription for the elderly (ACSM 2000), the ACSM references for
exercise programming for cancer patients (Schwartz 1997) and the
exercise prescription guidelines for early-stage cancer patients and
cancer survivors as recommended by Courneya (Courneya 2000).
We classified studies as trials with an adequate training stimulus
if they met three of four predefined requirements (see Table 3).
Each criterion was answered with ’yes’, ’no’ or ’n/a’ (not available);
answers scored as ’yes’ were coded as ’+’, ’no’ as ’-’ and ’n/a’ as ’?
’. A quality score was then calculated for each study by summing
scores for individual items, resulting in a possible score from 0
to 4. In trials using exercise interventions with both aerobic and
resistance modules we assessed training stimulus for each module
and then calculated the corresponding mean.
Classification of high quality training studies (HQTS)
Moderate and high quality studies, that provided an adequate
training stimulus were classified as high quality training studies.
Data analysis
Reliability
Inter-rater agreement for the overall methodological quality as-
sessment was measured using the intraclass correlation coefficient
(ICC) based on the two-way mixed model with measures of ab-
solute agreement (Shrout 1997). We described the level of relia-
bility for the ICC using categories suggested by Landis and Koch
(Landis 1977) for Kappa, as another measure of inter-rater agree-
ment. ICC values of 0.21 to 0.40 were considered as ’fair agree-
ment’, values from 0.41 to 0.60 as ’moderate agreement’, from
0.61 to 0.80 as ’substantial agreement’ and from 0.81 to 1.00 as
’almost perfect agreement’.
Statistical pooling
Outcome measurements were presented as continuous data across
included studies. As the first step, we extracted data on outcomes
in the format in which they were reported. For selected outcomes
we extracted group means for final values and change scores with
the corresponding measures of variability such as standard devia-
tions (SD) or confidence intervals (CI) and the number of partici-
pants on whom the outcome was assessed per group. Missing data
5Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
were requested from authors. In a subsequent step we transformed
data. If variability was presented by measures other than stan-
dard deviations we obtained standard deviations using standard
approaches for transforming data. We transformed confidence in-
tervals, t-values, and P values into standard deviations as described
in the Cochrane Handbook for Systematic Reviews of Interven-
tions (Deeks 2005); when F-statistics were reported for compar-
ing two groups, we transformed F-statistics into T-statistics using
the following formula: T=√
F and continued transforming the T-
statistic into standard deviations.
As a summary statistic for meta-analysis of continuous outcomes,
we either used the standardised mean difference (SMD) or the
weighted mean difference (WMD). We chose the standardised
mean difference in cases where different assessment instruments
measuring the same construct were used across studies (for exam-
ple for fatigue and physical fitness outcomes). We did not combine
final values and change scores in meta-analyses since the difference
in standard deviation does not reflect “differences in measurement
scale, but differences in the reliability of the measurements” (Deeks
2005). The instruments used for the particular outcomes as well as
the base for calculating summary statistics (final values or change
scores) are summarised in Table 4. As a summary statistic for di-
chotomous outcomes we chose the relative risk (RR). Nausea was
the only outcome that was analysed as a dichotomous outcome: for
every participant the nausea outcome was either improvement or
no improvement (no change or nausea worsened). The only study
that assessed nausea (Winningham 1988) compared three groups;
for calculating the summary statistic we compared the index exer-
cise intervention with the combined reference groups (placebo and
untreated control). For those outcomes with data available from
only one study, we calculated and presented a summary statistic
for this particular study.
We used the random-effects model to obtain the average effect of
exercise because, in addition to the presence of random error, dif-
ferences between exercise studies during adjuvant cancer treatment
can also result from real differences between study populations,
adjuvant cancer treatment and the training stimulus. The random-
effects model considers these additional sources of between-study
variability as well as within-study variability.
Inconsistency of results across studies was evaluated by the I2 statis-
tic; I2 describes the percentage of variability in the point estimates
that is due to heterogeneity rather than sampling error (Higgins
2002). Following Higgins (Higgins 2003), we considered I2 values
of 25% as indicating low heterogeneity, I2 values of 50% as indi-
cating moderate heterogeneity and I2 values of 75% as indicating
large heterogeneity.
One trial (Segal 2001) contributed to the meta-analysis of physical
functioning with two exercise groups: one group performed self-
directed exercise (referred to as Segal 2001 SD) and one group
attended supervised exercise sessions (referred to as Segal 2001SU).
We incorporated both exercise arms into the meta-analysis and
allocated a control group to each of them, as half the number of
participants and events observed in the control group.
R E S U L T S
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies; Characteristics of ongoing studies.
Through a comprehensive literature search, 1612 potentially rel-
evant references were identified and screened for retrieval. A total
of 1580 references were excluded based on the title and abstract
with 32 references retrieved for more detailed evaluation. From
these, 22 publications were excluded, one trial is awaiting assess-
ment (pending publication) and nine controlled clinical trials were
selected as appropriate to be included in the meta-analyses.
Excluded studies
The exercise intervention was not concurrent with adjuvant can-
cer treatment in six trials: exercise was either part of a complex
intervention or no exercise intervention was implemented in three
trials; in four trials the participants were not predominantly breast
cancer patients; five trials could not be characterised as controlled
trials (they were study protocols or reviews). Three more trials did
not compare two groups assigned by the investigator (they com-
pared high exercisers with low exercisers) and one trial did not
assess health-related outcome measures. For a detailed description
of the reasons for exclusion see the table of ’Characteristics of ex-
cluded studies’. Note that this table does not only contain clinical
studies but also review articles etc which were part of our full text
retrieval in order to assure our decision of exclusion when abstracts
were ambiguous.
Included studies
The final selection based on consensus resulted in nine trials being
included in this review. For trial characteristics and outcomes seethe table of ’Characteristics of included studies’.
Participants
The distinctive feature of each of the trials appeared to be the mode
of adjuvant cancer treatment received by the participants. Women
obtained different regimens of adjuvant treatment across these
nine exercise intervention studies: one trial (Segal 2001) included
patients on chemotherapy, radiotherapy or hormonal therapy; pa-
tients received either chemotherapy or radiotherapy in two trials
(Campbell 2005; Mock 2004); chemotherapy only in four trials
(Crowley 2003; MacVicar 1986; MacVicar 1989; Winningham
1988); and two trials (Drouin 2002; Mock 1997) included pa-
tients undergoing radiotherapy only.
Intervention
Mode of exercise differed across trials. Seven trials tested aero-
bic exercise interventions, with three trials using cycle ergometer
interval training (MacVicar 1986; MacVicar 1989; Winningham
1988) and four trials offering walking programmes (Drouin 2002;
6Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mock 1997; Mock 2004; Segal 2001). The remaining two trials
(Campbell 2005; Crowley 2003) applied a combined aerobic-re-
sistance programme which was implemented as a group exercise
programme in one of the trials (Campbell 2005).
Apart from one trial (Drouin 2002) that used a stretching inter-
vention as the comparison arm, trials compared an exercise inter-
vention with no intervention.
Exercise interventions lasted six to seven weeks for women un-
dergoing radiation treatment in three trials (Drouin 2002; Mock
1997; Mock 2004), 10 weeks in three trials (MacVicar 1986;
MacVicar 1989; Winningham 1988) and more than 12 weeks
for women undergoing chemotherapy treatment in four trials
(Campbell 2005; Crowley 2003; Mock 2004; Segal 2001). The
longest intervention period of any trial was 26 weeks (Segal 2001).
Trials with shorter intervention periods (six to seven weeks) were
those with breast cancer patients receiving radiation treatment,
which is of shorter duration than chemotherapy. In one trial (Mock
2004) the exercise intervention was implemented to span the pe-
riod of time from initiation to cessation of the participant’s ad-
juvant therapy and subsequently participants in the intervention
arm of the trial had intervention periods of variable length (either
six weeks with radiation treatment or three to six months with
chemotherapy).
In four trials (Campbell 2005; MacVicar 1986; MacVicar 1989;
Winningham 1988) and in one of the two intervention arms in one
further trial (Segal 2001) the exercise intervention was supervised;
participants’ exercise (walking) was self-directed in another four
trials (Crowley 2003; Drouin 2002; Mock 1997; Mock 2004) and
in the second intervention arm of Segal 2001.
Outcomes
Physical fitness and fatigue were the outcome measures most
frequently assessed, with eight trials measuring physical fitness
(Campbell 2005; Crowley 2003; Drouin 2002; MacVicar 1986;
MacVicar 1989; Mock 1997; Mock 2004; Segal 2001) and seven
studies measuring fatigue (Campbell 2005; Crowley 2003; Drouin
2002; MacVicar 1986; Mock 1997; Mock 2004) or vitality (Segal
2001), as a related construct. Other outcomes assessed were body
composition, quality of life, psychological distress, side effects re-
lated to adjuvant cancer treatment, immune functioning, adher-
ence and adverse effects. For detailed information on outcome
measures see the table of ’Characteristics of included studies’.
Other study characteristics
Small sample size was common among included trials. Only two
trials (Mock 2004; Segal 2001) had more than 30 participants per
group; sample size was based on power calculations in only three
trials (Mock 1997; Mock 2004; Segal 2001). The median sample
size was 42 patients, interquartile range (IQR) 22 to 82. Two trials
were controlled clinical trials (CCT) without random allocation of
women to intervention and control group (MacVicar 1986; Mock
1997); the other trials were randomised controlled trials.
Risk of bias in included studies
Methodological quality
For results of the methodological assessment see the table of
’Methodological scores’ (Table 5). The intraclass correlation coef-
ficient (ICC 0.82, 95% CI - 0.03 to 0.97) indicated an almost per-
fect agreement among the two review authors; all disagreements
could be resolved by discussion.
On average, the quality of the studies was moderate with a mean
quality score of 11 (range 7 to 14 points). The methodological
quality score was associated with year of publication. The mean
overall methodological score in the three studies published in the
1980s was 8.3, compared to a mean of 12.5 in the studies published
later than 1990.
The following methodological issues relating to the included stud-
ies are of special interest in exercise studies. Firstly, although feasi-
ble, lack of observer blinding was common and was attempted in
only one study (Crowley 2003), however, the success of blinding
activities was not evaluated in that study.
Secondly, adherence problems which would continue to occur in
routine practice are of concern. Non-adherence was included in
the estimated benefit of exercise in all studies by including non-
adherent participants in the intervention group to which they were
assigned. Mock (Mock 2004) applied an innovative valid statistical
analysis and estimated the complier average causal effect (CACE)
which maintains randomisation-based properties and addresses
non-adherence to the exercise intervention. Potentially long-term
side effects of adjuvant cancer treatment are fatigue and weight
gain and so long-term follow up was considered in our quality
score. However, none of the included studies assessed outcomes
beyond the period of adjuvant therapy. In two ongoing studies a
six-month follow up is planned (Courneya 2005; Mutrie 2005).
Analysis of training stimulus
The training stimulus was adequate in all included studies.
High quality training studies (HQTS)
Seven studies that had methodological quality scores of nine points
or greater and provided adequate exercise training stimuli were
classified as HQTS (Campbell 2005; Crowley 2003; Drouin 2002;
Mock 1997; Mock 2004; Segal 2001; Winningham 1988).
Effects of interventions
Effectiveness of exercise programmes
We performed meta-analyses for physical fitness, fatigue and body
composition (weight gain). Trials that were included in the meta-
analysis for cardiorespiratory fitness either measured performance,
for example distance walked in a given time, or maximum oxygen
uptake. Trials that were included in the meta-analysis for fatigue
predominantly applied the (revised) Piper fatigue scale. Moreover,
the symptom assessment scale (Mock 1997) and the vitality scale
of the 36-item short form (SF-36) of the Medical Outcomes Study
(MOS) (Segal 2001) were used as assessment instruments for fa-
7Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
tigue and vitality as a related construct, respectively.
Physical fitness
Five trials reported small but statistically significant improvements
in tests of cardiorespiratory fitness (Crowley 2003; Drouin 2002;
MacVicar 1989) or in physical performance assessed via timed
walking distances (Campbell 2005; Mock 1997). One controlled
clinical trial, a pilot study presented descriptive statistics only
(MacVicar 1986). In one trial (Segal 2001) improvements in car-
diorespiratory fitness (assessed via oxygen uptake) did not reach
statistical significance. However, improvement in physical func-
tioning (assessed via the physical functioning scale of the 36-
item short form (SF-36) of the Medical Outcomes Study (MOS)
reached statistical significance in the self-directed arm of this trial
(but not in the supervised arm). The authors’ interpretation of
these findings was that improvements in physical functioning (as
measured by the SF-36 physical functioning scale) may occur even
without changes in physiologic fitness measures (as measured by
oxygen uptake).
Meta-analysis of four trials yielding five comparisons (Campbell
2005; Drouin 2002; Mock 1997; Segal 2001 SD; Segal 2001SU)
provided some evidence that exercise improved cardiorespiratory
fitness: SMD 0.66, 95% CI 0.20 to 1.12 (see: Comparison and
data, figure 1). There was moderate heterogeneity with an I² of
54.7%. One trial (with two comparisons) predominantly con-
tributed to the heterogeneity and I2 was reduced to 0% when this
trial (Segal 2001) was excluded from the meta-analysis. Possible
causes for this finding are proposed in the Discussion section.
Two HQTS studies (Crowley 2003; Drouin 2002) evaluated
changes in muscular strength following aerobic exercise and aer-
obic-resistance exercise, respectively. In both trials no statistically
significant differences in strength were found and thus there is
no evidence that exercise is effective in increasing strength dur-
ing adjuvant cancer treatment. Data could be extracted from one
trial only (Drouin 2002): SMD -0.10, 95% CI -0.99 to 0.78 (seeComparison and data, figure 2).
Fatigue
Meta-analysis of five trials yielding six comparisons (Campbell
2005; Drouin 2002; Mock 1997; Mock 2004; Segal 2001 SD;
Segal 2001SU) found a statistically non-significant improvement
in fatigue for participants in the exercise intervention groups com-
pared to control (non-exercising) groups: SMD -0.12, 95% CI -
0.37 to 0.13 (see: Comparison and data, figure 3).
Body Composition
Several approaches for measuring the effects of exercise on body
composition were applied across studies, including body weight,
BMI, skinfold measurement and lean body mass. The result of
the meta-analysis of weight change was a statistically non-signif-
icant reduction in weight for participants in the aerobic exercise
intervention groups compared to a non-exercising control group:
SMD -1.11, 95% CI -2.44 to 0.22 (see: Comparison and data,
figure 4). One other trial (Drouin 2002) that also assessed weight
as an outcome could not be included in the meta-analysis since
only final values for weight were available.
Adherence and contamination
Different approaches were used among the included studies to
measuring adherence, that is, the level of exercise participation
achieved once the individual had agreed to undertake it. First, ad-
herence was assessed via the proportion of possible exercise ses-
sions attended by participants, on average; the total number of
possible exercise sessions resulted from frequencies per week that
ranged from two to five sessions. Second, adherence was assessed
as the proportion of adherent participants with cut-points of 60
and 90 minutes of exercise per week (Mock 1997; Mock 2004).
Adherence to exercise was said to be 70% or more of possible exer-
cise sessions (supervised or self-directed) in four trials (Campbell
2005; Crowley 2003; Drouin 2002; Segal 2001). Adherence may
be of a similar magnitude in one trial (MacVicar 1989) since they
let participants repeat missed sessions. The proportion of adher-
ent participants was 86% in (Mock 1997) and 72% in (Mock
2004). No information was given in the remaining two trials
(MacVicar 1986; Winningham 1988). Exercise levels in non-exer-
cising control groups (contamination) were reported in only two
trials (Crowley 2003; Mock 2004). Whereas Crowley 2003 stated
a significant difference in activity levels between the two groups
two groups in terms of frequency and duration of exercise, Mock
2004 observed 39% of the control group beginning regular walk-
ing during the study, at a level greater than 45 minutes per week,
which demonstrates considerable contamination. However, when
adopting the underlying cut-point of 45 minutes per week (Mock
2004), contamination can also be observed in the trial of Crowley
2003 (mean of 53 minutes per week walked in the control group).
Exercise adherence regarding exercise intensity was not reported
in any of the included trials; exercise adherence regarding duration
of single exercise sessions was reported in Mock 2004only.
Adverse effects
Adverse effects due to exercise were reported for six trials (
Campbell 2005; Crowley 2003; Drouin 2002; Mock 1997; Mock
2004; Segal 2001). Some adverse effects were observed in two tri-
als: Crowley (Crowley 2003) reported lymphedema in one par-
ticipant; Drouin (Drouin 2002) reported shoulder tendonitis and
decreases in strength due to overtraining in one participant. None
of the trials described how relevant information was collected or
whether surveillance of adverse effects was passive (spontaneously
reported by participants) or active (based on structured question-
naires or interviews).
Quality of life
Cancer- and cancer site-specific quality of life
Two HQTS (Campbell 2005; Segal 2001) examined effects of ex-
ercise on cancer- and cancer site-specific quality of life. Camp-
bell (Campbell 2005) found statistically significant differences be-
tween groups in general quality of life, particularly in physical and
functional subscales of the general version of the functional as-
sessment of cancer therapy scale (FACT-G). However, no statisti-
8Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
cally significant differences between groups were found for breast
cancer specific quality of life using the functional assessment of
cancer therapy scale for breast cancer patients (FACT-B). On the
other hand, no statistically significant differences between groups
were reported for either general or breast cancer specific quality of
life (FACT-G and FACT-B), over a 26 week intervention period,
in the trial of Segal (Segal 2001). Thus, evidence is conflicting as
to whether exercise interventions are effective in increasing can-
cer- and cancer site-specific quality of life. Data could be extracted
from one trial only (Campbell 2005): FACT G SMD 0.95, 95%
CI -0.01 to 1.91; FACT B SMD 0.78, 95% CI -0.16 to 1.72 (see:Comparison and data, figures 5 and 6).
Generic health-related quality of life
Generic health-related quality of life (assessed via MOS SF-36) was
examined by Segal (Segal 2001) and Crowley (Crowley 2003) and
no statistically significant differences between groups were found.
Thus, there is limited evidence for the effectiveness of exercise
programmes for generic health-related quality of life (assessed via
MOS SF-36) during breast cancer treatment. Quantitative syn-
thesis was not performed because only data for subscales, but no
data for physical and mental health summary measures, were pre-
sented.
Psychological distress outcomes: anxiety, mood, depression
Anxiety
Anxiety was reduced in one trial (Mock 1997) suggesting limited
evidence for the effects of exercise in reducing anxiety: SMD -
0.66, 95% CI -1.25 to - 0.06 (see: Comparison and data, figure
7).
Mood disturbances
There is no evidence for the effect of exercise on mood disturbances
with data from only one study that found no statistically significant
difference between groups (Drouin 2002): SMD -0.69, 95% CI
-1.60 to 0.22 (see: Comparison and data, figure 8).
Depression
There was only one trial that examined group differences for de-
pression and no statistically significant difference was found (Mock
1997): SMD -0.48, 95% CI -1.07 to 0.10 (see: Comparison and
data, figure 9). There is no evidence that exercise is effective in
reducing depression during adjuvant cancer treatment.
Other outcomes
No statistically significant differences between groups were found
for satisfaction with life (Campbell 2005), physical self-efficacy
and attention performance (Crowley 2003) as well as for satisfac-
tion with body (Mock 1997).
Biological outcomes
Immune functioning
Immune parameters (T-cells and natural killer cells) as well as ox-
idative stress were assessed in only one trial (Drouin 2002). No
statistically significant differences were observed during radiother-
apy (see: Comparison and data, figure 10, 11, 12). Thus, there
is no evidence for an effect of exercise programmes on immune
functioning during breast cancer treatment.
Other side effects relating to adjuvant cancer treatment: nausea
and sleep disturbances
Nausea was measured in one trial only (Winningham 1988); the
data from this trial show that moderate aerobic exercise may pro-
vide relief from the symptom of chemotherapy-associated nausea
in some patients. The relative risk (RR) for nausea relief was 4.33,
95% CI 1.34 to 13.99 (see: Comparison and data, figure 13). Thus,
there is limited evidence for an effect of exercise programmes on
reduction of nausea.
Sleep disturbances were reduced in one trial (Mock 1997) which
provided limited evidence for an effect of exercise programmes on
reduction of sleep disturbances: SMD -0.67, 95% CI -1.27 to -
0.08 (see: Comparison and data, figure 14).
D I S C U S S I O N
This review offers little evidence that women with breast cancer
may benefit through improved physical fitness from exercise dur-
ing adjuvant cancer treatment. Statistically significant improve-
ments for cardiorespiratory fitness, anxiety, sleep disturbance and
nausea relief were found. No statistically significant differences
were found for the other outcomes examined (fatigue, weight,
quality of life, depression, strength, immune function or mood).
However, these results are based on a small number of trials and
usable data could be extracted from only one study for the major-
ity of these outcomes. Only one of the two non-randomised tri-
als (Mock 1997) was included in quantitative analyses; results are
similar to those of randomised trials and do not appear to produce
any bias.
Limitations of the review
This review is based on a small number of small trials with limited
numbers of participants and with a considerable degree of clinical
heterogeneity between trials regarding adjuvant cancer treatment
and exercise intervention. It remains to be explored whether dif-
ferences in adjuvant cancer treatment and exercise intervention
actually affect results. In spite of our comprehensive attempts to
identify all relevant studies, predominantly English language stud-
ies were retrieved for inclusion in this review (one German trial is
awaiting assessment after its completion). This may reflect selec-
tive publication of English language studies with statistically sig-
nificant findings. The policy of registration of trials may provide
an interesting basis for addressing publication bias in the future
(Antes 2004).
The assessment of training stimulus was based on two scores, one
for aerobic and one for resistance exercise. For exercise interven-
tions with both aerobic and resistance modules, applicability of
these two single scores (developed for assessing training stimulus
9Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
of aerobic or resistance interventions only) may lead to the under-
estimation of the strength of the training stimulus.
Limitations of included studies
There was a clear trend toward a higher methodological quality in
studies published after 1990; this trend coincides with the devel-
opment of recommendations for the reporting of RCTs, for ex-
ample the CONSORT statement (Altman 2001). On the other
hand, the early studies are really pioneers in the field of exercising
during adjuvant cancer therapy. The effect of improved quality on
trial outcomes could not be assessed in this review due to limited
usable data from these trials.
Reporting of outcome measures
A wide range of outcome measures was assessed across the studies,
which made it difficult to combine outcomes in meta-analysis. For
example, psychosocial distress was assessed via mood, anxiety, de-
pression, satisfaction with life, satisfaction with body, self-efficacy
and sleep disturbances; and body composition was evaluated via
weight, body mass index (BMI), subcutaneous fat and lean body
mass. Moreover, data reporting was very poor and did not provide
estimates of effect size that could be pooled. Reporting of harms-
related data from exercise intervention trials during adjuvant can-
cer treatment also needs improvement.
Statistical power
Benefits of exercise interventions may be relatively small. Sub-
sequently, the number of participants included should be great
enough for allowing the detection of small differences between
groups. The sample sizes in the included studies ranged from 6 to
60 in the intervention group.
Analysis of training stimulus
The individual’s level of fitness is an important factor to consider
before determining the level of exercise intensity (ACSM 2000).
According to ACSM (ACSM 2000), deconditioned individuals
may demonstrate increases in their cardiorespiratory fitness with
exercise intensities at the lower end of the intensity continuum;
whereas more fit individuals need to work at the higher end of the
intensity continuum to improve fitness. The initial fitness level
was considered in three studies only, which limited participation
to sedentary individuals; however, definitions of sedentary varied.
Adherence and contamination
For sedentary individuals, a change in personal health behaviour
is required in order to take up regular exercise. Thus, any exercise
intervention can additionally be evaluated according to the degree
of behavioural change achieved in the intervention group; a lack
of adherence can compromise the training stimulus as well as the
sustainability of exercise behaviour. According to the American
College of Sports Medicine (ACSM 2000) the art of exercise pre-
scription is the “successful integration of exercise science with be-
havioral techniques that result in long-term program compliance”.
Only one trial (Campbell 2005) applied theory-based methods
focused on changing behaviour. Adherence problems do not only
arise in terms of participation in exercise sessions and frequency
of sessions but also in terms of the training intensity and duration
actually achieved during each exercise session. Insufficient exercise
intensity or duration may compromise the training stimulus as a
whole. However, these two facets of the training stimulus were
poorly evaluated and reported in the included studies.
Besides adherence, the extent to which the control group performs
exercise (contamination) is a second critical component in exercise
studies. Exercise contamination is rarely reported and often only
when the exercise programme is home based.
Results
Physical fitness
Moderate heterogeneity across studies was observed for physical
fitness outcomes. It was one trial that predominantly contributed
to this heterogeneity (Segal 2001). The trial characteristics that
may have contributed to the heterogeneity were as follows. The
exercise intensity of 50 to 60% maximum heart rate was rather low
and may have resulted in a modest effect that was not statistically
significant; the intervention period was relatively long (26 weeks)
compared with other trials included in this meta-analysis, possibly
resulting in the cumulative side effects of cancer treatment over
time counteracting the physiological exercise response. Regarding
muscular strength, there was no evidence for positive effects of ex-
ercise. However, in Drouin (Drouin 2002) the intervention (walk-
ing) was not intended to produce effects on this outcome (mus-
cular strength in upper extremities) and subsequently the effect of
exercise on muscular strength should be evaluated in future trials.
Fatigue
Additional exercise studies are required to assess the effect of exer-
cise on cancer-related fatigue.
A U T H O R S ’ C O N C L U S I O N S
Implications for practice
Receiving adjuvant treatment for breast cancer should no longer
be seen as a rigid contraindication for exercise, which should be
regarded as a feasible, supportive self-care intervention. Based on
current evidence, improvement can be expected in physical fitness
and the resulting capacity for performing activities of daily life.
An improvement for other outcome variables is still tenable, due
to a lack of evidence.
Exercise adherence during cancer treatment constitutes a challenge
and thus programmes are needed to foster exercise participation.
For behaviour changes to occur (the adoption of regular exercise in
this instance) it is essential that intervention programmes focus on
10Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
underlying principles from theories about why people change their
behaviours. The social cognitive theory appears to be a promising
theoretical framework for promoting exercise behaviour in breast
cancer patients (Pinto 2002; Rogers 2004; Rogers 2005). The key
construct in the social cognitive theory is self-efficacy. Exercise self-
efficacy can be described either as the confidence to overcome bar-
riers to exercise or as confidence in the ability to perform certain
exercise tasks. Self-efficacy has proven to be an important corre-
late of exercise among breast cancer patients. Exercise self-efficacy
among breast cancer patients during cancer treatment is reported
as lowest when patients are nauseated, tired, not interested, lack-
ing time and lacking exercise enjoyment (Rogers 2006).
Future exercise interventions should target the exercise barriers.
Exercise enjoyment, for example, may be addressed through pick-
ing up recent trends in the field of fitness, such as Pilates, Nordic
walking, Tai Chi, step aerobics and dancing; of course adequately
adjusted to the needs and limitations of the target group. Group
exercise or partner assisted exercises may also increase exercise en-
joyment. Time management may be addressed by exercise classes
taking place in different locations, choosing venues that are ac-
cessible by public transport and by timetabling classes at various
times in the day and evening.
Implications for research
At this stage there is a lack of evidence for relevant benefits of
exercise as well as for harms. Results of ongoing trials have to be
awaited and further trials with adequate power are needed.
Consensus of researchers on outcome measures for exercise stud-
ies involving breast cancer patients receiving adjuvant treatment
is needed in order to facilitate interpretation and comparison of
results across various interventions. The long-term follow up of
exercise interventions requires attention because some side effects
of adjuvant cancer treatment are either long term, such as fatigue
or deconditioning, or may be related to recurrence and mortality,
such as weight gain. Besides health related outcome measures, ad-
herence and contamination as well as potential harms should be
assessed and reported. Reporting standards for harms (Ioannidis
2004) should help to inform practitioners and the public on poten-
tial harms of exercise interventions during adjuvant cancer treat-
ment.
As described above, the actual training stimulus may substantially
deviate from the assigned exercise regimen. If participants allo-
cated to the exercise group do not exercise (non-adherence), and
at the same time participants allocated to the control group do
exercise (contamination), the originally intended trial groups are
distorted into groups with participants who exercise and those who
do not (moreover in unknown proportions). If those groups are
analysed as ’randomised’, effects may be underestimated. In effi-
cacy trials investigators need to ensure adherence to the interven-
tion to determine whether exercise interventions in this popula-
tion work. Subsequently, exercise programmes should be designed
to address exercise facilitators such as exercise enjoyment; this may
be achieved by offering a variety of alternating exercise modes that
assure an adequate training stimulus. Inclusion of sedentary par-
ticipants only may be a way to deal with contamination issues,
utilising the observation that physical activity and exercise decline
during cancer treatment (Irwin 2003). In effectiveness trials, we
recommend that both adherence and contamination are reported
as an outcome measure because poor adherence can render an ef-
ficacious intervention ineffective. As a format for reporting adher-
ence we regard the following specification as helpful: the propor-
tion of participants who achieved a cut-point of 60 minutes of
moderate to strenuous exercise per week.
Finally, regarding recruitment problems and thus the problem of
small sample sizes, multi-site trials may be advisable.
A C K N O W L E D G E M E N T S
We would like to thank Sharon Parker who rendered assistance in
her role as Assistant Review Group Coordinator of the Cochrane
Breast Cancer Group and the Editorial Base of the Cochrane Breast
Cancer Group. Moreover, we would like to thank the referees who
provided valuable feedback during the peer review process, the
authors of primary trials for additional information about their
trials and the expert who contributed to identifying studies for
inclusion. Anne Franke and Horst Müller rendered support in
statistics and Katja Borodulin assisted with one Finish language
publication.
11Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
R E F E R E N C E S
References to studies included in this review
Campbell 2005 {published data only}
Campbell A, Mutrie N, White F, McGuire F, Kearney N.
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Winningham ML, MacVicar MG, Bondoc M, Anderson
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JA, Haisfield Wolfe ME, et al.Effects of exercise on fatigue,
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J, et al.Structured exercise improves physical functioning
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J, et al.Structured exercise improves physical functioning
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Segal 2001SU {published and unpublished data}
Segal R, Evans W, Johnson D, Smith J, Colletta S, Gayton
J, et al.Structured exercise improves physical functioning
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Winningham 1988 {published data only}
Winningham ML, MacVicar MG. The effect of aerobic
exercise on patient reports of nausea. Oncology Nursing
Forum 1988;15(4):447–50.
References to studies excluded from this review
Burnham 2002 {published data only}
Burnham TR, Wilcox A. Effects of exercise on physiological
and psychological variables in cancer survivors. Medicine
and Science in Sports and Exercise 2002;34(12):1863–7.
Courneya 2003a {published data only}
Courneya KS, Friedenreich CM, Sela RA, Quinney HA,
Rhodes RE, Handman M. The group psychotherapy and
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Fairey AS. Randomized controlled trial of exercise training in
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Demark-Wahnefried W. Randomized study of a diet
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exercise and diet (Project LEAD): intervening to improve
function among older breast and prostate cancer survivors.
Controlled Clinical Trials 2003;24(2):206–23.
Dimeo 1999 {published data only}
Dimeo FC, Stieglitz RD, Novelli-Fischer U, Fetscher
S, Keul J. Effects of physical activity on the fatigue and
psychologic status of cancer patients during chemotherapy.
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Fairey 2003 {published data only}
Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW,
Mackey JR. Effects of exercise training on fasting insulin,
insulin resistance, insulin-like growth factors, and insulin-
like growth factor binding proteins in postmenopausal
breast cancer survivors: a randomized controlled trial.
Cancer Epidemiology, Biomarkers & Prevention 2003;12(8):
721–7.
12Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Given 2002 {published data only}
Given B, Given C, McCorkle R, Kozachik S, Cimprich
B, Rahbar M, Wojcik C. Pain and Fatigue Management:
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Ho 1986 {published data only}
Ho C. Psychological adaptation and coping resources
of breast cancer patients: Comparisons across three
treatment modalities. Dissertation-Abstracts-International.
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1986; Vol. 47:2617.
Latikka 1997 {published data only}
Latikka P, Pukkala E, Vihko V. [Exercise and breast cancer].
Duodecim 1997;113(4):317–22.
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McKenzie DC, Kalda AL. Effect of upper extremity exercise
on secondary lymphedema in breast cancer patients: a pilot
study. Journal of Clinical Oncology 2003;21(3):463–6.
Mock 1994 {published data only}
Mock V, Burke MB, Sheehan P, Creaton EM, Winningham
ML, McKenney Tedder S, Schwager LP, Liebman M. A
nursing rehabilitation program for women with breast
cancer receiving adjuvant chemotherapy. Oncology Nursing
Forum 1994;21(5):899–907.
Mock 2001 {published data only}
Mock V, Pickett M, Ropka ME, Muscari Lin E, Stewart
KJ, Rhodes VA, et al.Fatigue and quality of life outcomes
of exercise during cancer treatment. Cancer Practice 2001;9
(3):119–27.
Mock 2002 {published data only}
Mock V. Fatigue and physical functioning during breast
cancer treatment. Oncology Nursing Forum 2002;29(?):338.
Mustian 2002 {published data only}
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therapy for breast cancer rehabilitation. In: Hall RL editor
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modalities and assessing outcomes. NY: Haworth Press, 2002:
105–18.
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Pinto 2003 {published data only}
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Psychological and fitness changes associated with
exercise participation among women with breast cancer.
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Schwartz 1999 {published data only}
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quality of life. Quality of Life Research 1999;8(6):529–38.
Schwartz 2001 {published data only}
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reduces daily fatigue in women with breast cancer receiving
chemotherapy. Medicine and Science in Sports and Exercise
2001;33(5):718–23.
Segar 1998 {published data only}
Segar ML, Katch VL, Roth RS, Garcia AW, Portner TI,
Glickman SG, Haslanger S, Wilkins EG. The effect of
aerobic exercise on self-esteem and depressive and anxiety
symptoms among breast cancer survivors. Oncology Nursing
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Shaw 2003 {published data only}
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Wilkie 2003 {published data only}
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Public Health Association, 131st. Annual Meeting. 2003.
References to studies awaiting assessment
Battaglini 2004 {published data only}
Battaglini CLLG. A randomized study on the effects of a
prescribed exercise intervention on lean mass and fatigue
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References to ongoing studies
Chetiyawardana 2004 {published data only}
Chetiyawardana AD. A pilot study to investigate the
effects on fitness and quality of life of an individualised
exercise programme for breast cancer patients undergoing
radiotherapy. http://www.controlledtrials.com/isrctn/trial/
%7C/0/26140710.html 2004.
Courneya 2005 {unpublished data only}
Courneya K, Segal R, McKenzie D, Mackey J, Friedenreich
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Kleine-Tebbe 2006 {unpublished data only}
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13Exercise for women receiving adjuvant therapy for breast cancer (Review)
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15Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included studies [ordered by study ID]
Campbell 2005
Methods RCT, 2 groups, computer-generated numbers, stratification by adjuvant cancer treatment
Participants 22 breast cancer patients, after surgery, receiving chemotherapy or radiotherapy
Interventions Group exercise: aerobic and resistance training (walking, cycling, low-level aerobics, muscle-strengthening
exercises, circuits),
behaviour change communication, supervised,
60 - 75% HRmax,
10 - 20 min per session exercise, plus warm-up, cool-down, relaxation,
2/week,
12 weeks.
Control: no intervention.
Outcomes Quality of life (cancer specific, cancer site-specific),
fatigue,
physical performance,
physical activity,
expectation of treatment,
satisfaction with life.
Notes Methodological quality score: 13.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear B - Unclear
Crowley 2003
Methods RCT, 2 groups, random numbers table; Intention-to-treat analysis
Participants 22 breast cancer patients, stage I, II; after surgery, receiving adjuvant chemotherapy (Adriamycin, Cytoxan)
Interventions Aerobic training (walking) and resistance training (tubing),
self-directed,
Aerobic training: 60% of HRmax, 20 - 60 min. per session, 3 - 5 d/week, 13 weeks.
Resistance training: 12 - 15 repetitions, ca. 20 min, 1 - 2 sets, 2 - 3 d/week, 13 weeks
Control: no intervention.
16Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Crowley 2003 (Continued)
Outcomes Cardiorespiratory fitness,
muscular fitness,
fatigue,
physical self-efficacy,
attention performance,
functional wellness,
quality of life,
physical activity.
Notes Methodological quality score: 13.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Yes A - Adequate
Drouin 2002
Methods RCT, 2 groups, random number chart.
Participants 23 breast cancer patients, stages 0 - III; after surgery, receiving radiotherapy, sedentary
Interventions Aerobic training (walking), self-directed,
50 - 70 % HRmax
20 - 45 min per session,
3 - 5/week,
7 weeks.
Control: Stretching, 3 - 5/week, 7 weeks.
Outcomes Fatigue,
cardiorespiratory fitness,
muscular fitness,
mood,
body composition,
immune function (CD4+/ CD8+ ratio, natural killer cytotoxic activity) ,
oxidative stress (8-isoprostane).
Notes Methodological quality score: 12.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
17Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Drouin 2002 (Continued)
Allocation concealment? Yes A - Adequate
MacVicar 1986
Methods CCT, 2 groups.
Participants 10 breast cancer patients, after surgery, receiving chemotherapy
Interventions Aerobic training (cycling, interval training),
60 - 85% HRmax,
20 - 30min per session,
3/week,
10 weeks.
Control: no intervention.
Outcomes Cardiorespiratory fitness,
mood.
Notes Only descriptive statistics presented.
Methodological quality score: 7.
Training stimulus: adequate.
High quality training study: no.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear D - Not used
MacVicar 1989
Methods RCT, 3 groups, stratified by functional capacity.
Participants 45 breast cancer patients, stage II; after surgery, receiving chemotherapy
Interventions (1) Aerobic training (cycling, interval training),
60 - 85% HRmax,
20 - 30 min per session,
3 /week,
10 weeks.
(2) Control 1:
flexibility and stretching exercises.
(3) Control 2: no intervention.
Outcomes Cardiorespiratory fitness,
Body composition (described in Winningham 1989) via secondary analysis, comparing intervention to
no intervention group with n=24)
18Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
MacVicar 1989 (Continued)
Notes Description includes Winningham 1989 (2 publications).
Methodological quality score: 8.
Training stimulus: adequate.
High quality training study: no.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear B - Unclear
Mock 1997
Methods CCT, 2 groups, alternating assignment.
Participants 46 breast cancer patients, stages I and II; after surgery, receiving radiotherapy
Interventions Aerobic training (walking),
self-directed,
Rate of perceived exertion: 11 - 13,
20 - 30 min per session,
4 - 5/week,
6 weeks.
Control: no intervention.
Outcomes Physical activity,
fatigue,
physical performance,
emotional distress,
symptom experience: sleep disturbances, depression, anxiety, satisfaction with body
Notes Methodological quality score: 10.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear D - Not used
19Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mock 2004
Methods RCT, 2 groups, computer-generated randomisation; Complier Average Causal Effect (CACE); Intention-
to-treat effect of assignment that focuses only on ’full compliers’
Participants 119 breast cancer patients, stages 0 - III, after surgery, receiving chemotherapy or radiotherapy, sedentary
Interventions Aerobic training (walking), self-directed,
50 - 70% HR max,
15 min per session, increased to 30 min as training progressed,
5 - 6 /week,
radiotherapy: 6 weeks exercise;
chemotherapy: 3 - 6 month exercise.
Control: no intervention.
Outcomes Fatigue,
physical performance,
physical activity.
Notes Methodological quality score: 14.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Yes A - Adequate
Segal 2001
Methods RCT, 3 groups.
Participants n=123.
Interventions (1) ’Segal 2001 SD’ performed self-directed aerobic training; (2) ’Segal 2001 SU’ performed supervised
training;
(3) Control group.
Outcomes Generic and cancer-, cancer site-specific quality of life,
cardiorespiratory fitness,
body composition.
Notes Trial compared 2 exercise groups (self-directed and supervised) to 1 control group;
for meta-analysis control group was split into halves in order to compare with the particular intervention
group.
Described separately in Segal 2001 SD and Segal 2001 SU
Risk of bias
20Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Segal 2001 (Continued)
Item Authors’ judgement Description
Allocation concealment? Yes A - Adequate
Segal 2001 SD
Methods RCT, 2 groups (total: 3 groups), random numbers table; Intention-to-treat analysis
Participants 60 (total: n=123) breast cancer patients, stages I and II, receiving radiotherapy or hormonal therapy or
chemotherapy
Interventions IIntervention (n=40): self-directed aerobic training (walking),
50 - 60% VO2max,
35 - 40 min per session (including warm-up, walking, cool down),
5/weeks,
26 weeks.
Control (n=20): no intervention.
Outcomes Generic and cancer-, cancer site-specific quality of life,
cardiorespiratory fitness,
body composition.
Notes Methodological quality score: 13.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Yes A - Adequate
Segal 2001SU
Methods RCT, 2 groups (total: 3 groups), random numbers table; Intention-to-treat analysis
Participants 63 (total: n=123) breast cancer patients, stages I and II, receiving radiotherapy or hormonal therapy or
chemotherapy
Interventions Intervention (n=42): supervised aerobic training (walking), supervised,
50 - 60% VO2max,
35 - 40 min per session (including warm-up, walking, cool down),
5/weeks,
26 weeks.
Control (n=21): no intervention.
21Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Segal 2001SU (Continued)
Outcomes Generic and cancer-, cancer site-specific quality of life,
cardiorespiratory fitness,
body composition.
Notes Methodological quality score: 13.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Yes A - Adequate
Winningham 1988
Methods RCT, 3 groups; Intention-to-treat analysis.
Participants 42 breast cancer patients, after surgery, receiving chemotherapy
Interventions Aerobic training (cycling, interval training),
60 - 85% HRmax,
20 - 30min per session,
3/week,
10 weeks.
Control 1: no intervention.
Control 2: mild stretching, conversation, 1/week.
Outcomes Nausea,
somatisation.
Notes Methodological quality score: 10.
Training stimulus: adequate.
High quality training study: yes.
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear B - Unclear
HRmax: maximum heart rate
VO2max: maximal oxygen uptake
22Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Burnham 2002 Exercise intervention not concurrent with adjuvant cancer treatment
Courneya 2003a Participants not predominantly breast cancer patients (40%), exercise as part of a complex intervention
(group psychotherapy plus exercise)
Courneya 2003b Exercise intervention not concurrent with adjuvant cancer treatment (<50 % under current hormone
therapy)
Demark-Wahnefried 02 No clinical trial, protocol status,
exercise as part of a complex intervention (diet and exercise based counseling program)
Demark-Wahnefried 03 No clinical trial, design paper
Dimeo 1999 Participants not predominantly breast cancer patients (cancer patients with solid tumors and lymphomas)
,
no chemotherapy, radiotherapy or hormonal treatment (high dose chemotherapy followed by peripheral
stem cell transplantation)
Fairey 2003 Exercise intervention not concurrent with adjuvant cancer treatment
Given 2002 Participants not predominantly breast cancer patients (BC stages 0 - IV; colon and lung cancer),
no exercise intervention
Ho 1986 No exercise intervention
Latikka 1997 No clinical trial, review
McKenzie 2003 Intervention and adjuvant treatment not concurrent
Mock 1994 Exercise as part of a complex intervention (walking plus support group)
Mock 2001 Trial does not compare two groups as assigned by investigator
Mock 2002 No exercise intervention
Mustian 2002 No clinical trial, review
Pickett 2002 No health-related outcome measure (adherence study)
Pinto 2003 Exercise intervention not concurrent with adjuvant cancer treatment
Schwartz 1999 Trial does not compare two groups as assigned by investigator
Schwartz 2001 Trial does not compare two groups as assigned by investigator
23Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Segar 1998 Exercise intervention not concurrent with adjuvant cancer treatment
Shaw 2003 No clinical trial, protocol status,
exercise as part of a complex intervention (calcium-rich diet and exercise)
Wilkie 2003 Participants not predominantly breast cancer patients (63% female),
duration of intervention programme 4 weeks
Characteristics of ongoing studies [ordered by study ID]
Chetiyawardana 2004
Trial name or title A pilot study to investigate the effects on fitness and quality of life of an individualised exercise programme
for breast cancer patients undergoing radiotherapy
Methods
Participants 10 breast cancer patients, receiving a 3 week course of radiotherapy at the Queen Elizabeth Hospital, University
Hospital Birmingham Trust
Interventions Intervention: individualised exercise programme;
Control: no intervention.
Outcomes Fitness, quality of life (the European Organisation for Research and Treatment of Cancer - EORTC QLQ-
C3O, version 3)
Starting date November 2003
Contact information Dr A D Chetiyawardana
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
+44 (0)121 472 1311
Notes
Courneya 2005
Trial name or title Comparison of aerobic versus resistance exercise training in enhancing quality of life in early stage breast
cancer survivors receiving chemotherapy: A multicentre randomized trial
Methods
Participants 210 post-surgical breast cancer survivors scheduled for adjuvant chemotherapy
24Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Courneya 2005 (Continued)
Interventions Intervention: Aerobic training,
Resistance training, 12 - 24 weeks,
Control: no intervention (waiting list).
Outcomes Psychosocial well-being (e.g. fatigue, depression, anxiety, self-esteem), QOL (physical, functional, emotional,
social, and spiritual well-being), and physical fitness (i.e., cardiovascular endurance, muscular endurance,
body composition)
Starting date
Contact information Courneya, Kerry
1Faculty of Physical Education, University of Alberta
Notes six months follow-up!
Kleine-Tebbe 2006
Trial name or title Influence of aerobic exercise compared to relaxation training for women with breast cancer during adjuvant
chemotherapy
Methods
Participants 33 breast cancer patients receiving chemotherapy
Interventions Intervention: Aerobic training (walking), supervised, 24 weeks; 3/week, 20 - 25 min.
Control: Relaxation training
Outcomes Cardiorespiratory fitness, fatigue, body composition, quality of life, anxiety, depression, immune functioning
Starting date December 2003
Contact information Anke Kleine-Tebbe, Ph.D, Brustzentrum Charite, Campus Virchow Klinikum, Augustenburger Platz 1,
13353 Berlin
Notes
Mutrie 2005
Trial name or title A randomised controlled trial of a supervised exercise programme as a rehabilitation treatment for women
receiving early stage breast cancer treatment
Methods
Participants 182 breast cancer patients, receiving chemotherapy or radiotherapy
25Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mutrie 2005 (Continued)
Interventions Intervention: 12 week supervised exercise programme,
50 - 75% age-adjusted HRmax,
10 - 20 min plus warm-up, cool-down and relaxation,
2/week .
Control: usual care and monitoring.
Outcomes General quality of life (FACT-G), breast-specific quality of life (FACT-B), fatigue (FACT-F), endocrine
symptoms (FACT-ES), depression (BDI), mood (PANAS), physical performance (12 minute walking test),
physical activity (SPAQ), body composition (BMI), perceived expectations and benefits
Starting date
Contact information Anna Campbell Ph.D
Cancer Research UK Physical Activity Study
Strathclyde University (Jordanhill Campus)
Pesoe Building,
76 Southbrae Drive,
Glasgow G13 1PP
Phone:44-141-950-3137
a.m.campbell@strath.ac.uk
Anna Campbell Ph.D
Cancer Research UK Physical Activity Study
Strathclyde University (Jordanhill Campus)
Pesoe Building,
76 Southbrae Drive,
Glasgow G13 1PP
Phone:44-141-950-3137
a.m.campbell@strath.ac.uk
Notes six months follow-up!
26Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D A T A A N D A N A L Y S E S
Comparison 1. Exercise versus control
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Cardiorespiratory fitness 5 207 Std. Mean Difference (IV, Random, 95% CI) 0.66 [0.20, 1.12]
2 Strength 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
3 Fatigue 6 317 Std. Mean Difference (IV, Random, 95% CI) -0.12 [-0.37, 0.13]
4 Weight change 3 147 Mean Difference (IV, Random, 95% CI) -1.11 [-2.44, 0.22]
5 Cancer specific quality of life 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
6 Cancer site-specific quality of life 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
7 Anxiety 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
8 Mood disturbance 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
9 Depression 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
10 Natural killer cells 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
11 T-cells 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
12 Oxidative stress 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
13 Nausea relief 1 Risk Ratio (M-H, Random, 95% CI) Totals not selected
14 Sleep disturbances 1 Std. Mean Difference (IV, Random, 95% CI) Totals not selected
Analysis 1.1. Comparison 1 Exercise versus control, Outcome 1 Cardiorespiratory fitness.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 1 Cardiorespiratory fitness
Study or subgroup Exercise Control
Std.Mean
Difference Weight
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Campbell 2005 10 1423 (261) 9 1083 (176) 12.9 % 1.44 [ 0.41, 2.48 ]
Drouin 2002 13 22.6 (6.2) 8 16.6 (2.2) 14.3 % 1.13 [ 0.17, 2.09 ]
Mock 1997 22 3371 (300.46) 22 3089 (300.46) 22.3 % 0.92 [ 0.30, 1.55 ]
Segal 2001 SD 40 26.3 (5.3) 20 25.1 (6.1) 25.0 % 0.21 [ -0.33, 0.75 ]
Segal 2001SU 42 26.2 (5.1) 21 25.1 (6.1) 25.4 % 0.20 [ -0.33, 0.72 ]
Total (95% CI) 127 80 100.0 % 0.66 [ 0.20, 1.12 ]
Heterogeneity: Tau2 = 0.14; Chi2 = 8.83, df = 4 (P = 0.07); I2 =55%
Test for overall effect: Z = 2.81 (P = 0.0049)
-4 -2 0 2 4
Favours Control Favours exercise
27Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.2. Comparison 1 Exercise versus control, Outcome 2 Strength.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 2 Strength
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Drouin 2002 13 31.3 (6.5) 8 32 (6.4) -0.10 [ -0.99, 0.78 ]
-4 -2 0 2 4
Favours control Favours exercise
Analysis 1.3. Comparison 1 Exercise versus control, Outcome 3 Fatigue.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 3 Fatigue
Study or subgroup Exercise Control
Std.Mean
Difference Weight
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Campbell 2005 10 2.43 (1.94) 9 4.35 (3.48) 6.9 % -0.66 [ -1.59, 0.27 ]
Drouin 2002 13 3.4 (1.9) 8 3.9 (2.4) 7.6 % -0.23 [ -1.11, 0.66 ]
Mock 1997 22 26.12 (20.27) 24 43.05 (36.37) 15.7 % -0.56 [ -1.15, 0.03 ]
Mock 2004 54 3.5 (2.4) 54 3.7 (2.6) 32.1 % -0.08 [ -0.46, 0.30 ]
Segal 2001 SD 40 -60.8 (23.5) 20 -61.6 (17.7) 18.5 % 0.04 [ -0.50, 0.57 ]
Segal 2001SU 42 -55.8 (24) 21 -61.6 (17.7) 19.1 % 0.26 [ -0.27, 0.78 ]
Total (95% CI) 181 136 100.0 % -0.12 [ -0.37, 0.13 ]
Heterogeneity: Tau2 = 0.01; Chi2 = 5.83, df = 5 (P = 0.32); I2 =14%
Test for overall effect: Z = 0.93 (P = 0.35)
-4 -2 0 2 4
Favours exercise Favours control
28Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 Exercise versus control, Outcome 4 Weight change.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 4 Weight change
Study or subgroup Exercise ControlMean
Difference WeightMean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
MacVicar 1989 12 0.82 (2.1) 12 1.99 (2.1) 63.0 % -1.17 [ -2.85, 0.51 ]
Segal 2001 SD 40 0.4 (3.71) 20 0.6 (6.21) 20.4 % -0.20 [ -3.15, 2.75 ]
Segal 2001SU 42 -1.4 (6.28) 21 0.6 (6.21) 16.7 % -2.00 [ -5.27, 1.27 ]
Total (95% CI) 94 53 100.0 % -1.11 [ -2.44, 0.22 ]
Heterogeneity: Tau2 = 0.0; Chi2 = 0.65, df = 2 (P = 0.72); I2 =0.0%
Test for overall effect: Z = 1.63 (P = 0.10)
-10 -5 0 5 10
Favours exercise Favours control
Analysis 1.5. Comparison 1 Exercise versus control, Outcome 5 Cancer specific quality of life.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 5 Cancer specific quality of life
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Campbell 2005 10 11.9 (13.8) 9 -2.9 (16.1) 0.95 [ -0.01, 1.91 ]
-4 -2 0 2 4
Favours control Favours exercise
29Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.6. Comparison 1 Exercise versus control, Outcome 6 Cancer site-specific quality of life.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 6 Cancer site-specific quality of life
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Campbell 2005 10 14.3 (19.8) 9 -1.7 (19.4) 0.78 [ -0.16, 1.72 ]
-4 -2 0 2 4
Favours control Favours exercise
Analysis 1.7. Comparison 1 Exercise versus control, Outcome 7 Anxiety.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 7 Anxiety
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Mock 1997 22 10.44 (24.7) 24 26.93 (24.7) -0.66 [ -1.25, -0.06 ]
-4 -2 0 2 4
Favours exercise Favours control
30Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.8. Comparison 1 Exercise versus control, Outcome 8 Mood disturbance.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 8 Mood disturbance
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Drouin 2002 13 5.1 (22.1) 8 23.9 (32) -0.69 [ -1.60, 0.22 ]
-4 -2 0 2 4
Favours exercise Favours control
Analysis 1.9. Comparison 1 Exercise versus control, Outcome 9 Depression.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 9 Depression
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Mock 1997 22 9.51 (23.5) 24 21.05 (23.5) -0.48 [ -1.07, 0.10 ]
-4 -2 0 2 4
Favours exercise Favours control
31Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.10. Comparison 1 Exercise versus control, Outcome 10 Natural killer cells.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 10 Natural killer cells
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Drouin 2002 13 8.5 (9.2) 8 6.6 (4.2) 0.24 [ -0.65, 1.12 ]
-4 -2 0 2 4
Favours control Favours exercise
Analysis 1.11. Comparison 1 Exercise versus control, Outcome 11 T-cells.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 11 T-cells
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Drouin 2002 13 2.5 (1.1) 8 1.8 (1) 0.63 [ -0.27, 1.54 ]
-4 -2 0 2 4
Favours control Favours exercise
32Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.12. Comparison 1 Exercise versus control, Outcome 12 Oxidative stress.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 12 Oxidative stress
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Drouin 2002 10 244 (132.6) 5 316.4 (118.3) -0.53 [ -1.63, 0.57 ]
-4 -2 0 2 4
Favours exercise Favours control
Analysis 1.13. Comparison 1 Exercise versus control, Outcome 13 Nausea relief.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 13 Nausea relief
Study or subgroup Exercise Control Risk Ratio Risk Ratio
n/N n/N
M-H,Random,95%
CI
M-H,Random,95%
CI
Winningham 1988 8/16 3/26 4.33 [ 1.34, 13.99 ]
0.01 0.1 1 10 100
Favours control Favours exercise
33Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.14. Comparison 1 Exercise versus control, Outcome 14 Sleep disturbances.
Review: Exercise for women receiving adjuvant therapy for breast cancer
Comparison: 1 Exercise versus control
Outcome: 14 Sleep disturbances
Study or subgroup Exercise Control
Std.Mean
Difference
Std.Mean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Mock 1997 22 12.38 (29.5) 24 32.58 (29.5) -0.67 [ -1.27, -0.08 ]
-4 -2 0 2 4
Favours exercise Favours control
A D D I T I O N A L T A B L E S
Table 1. Eligibility assessment
Eligibility criteria
1. Number of groups involved in the trial (at least two groups required);
2. Proportion of patients with breast cancer (> 80% breast cancer patients required);
3. Intervention examined (exercise training);
4. Time of exercise training (concurrent with adjuvant treatment);
5. Duration of exercise intervention (at least six weeks) and
6. Type of outcomes as specified.
Table 2. Methodological quality assessment tool
Quality criteria
1.Were the eligibility criteria specified?
2.Was a method of randomisation performed?
3.Was the treatment allocation concealed?
4.Were groups similar at baseline?
5.Were interventions explicitly described?
6.Were co-interventions either avoided or comparable?
7.Was adherence acceptable in all groups?
8.Was the outcome assessor blinded to the intervention?
9.Were outcome measures relevant?
10.Were adverse effects described?
11.Was the withdrawal/ drop-out rate acceptable and were reasons described?
12.Was short-term follow-up measurement performed?
13.Was long-term follow-up measurement performed?
14.Was timing of outcome assessment comparable in both groups?
34Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 2. Methodological quality assessment tool (Continued)
15.Was the sample size described for each group at randomisation?
16.Did the analysis include intention-to-treat analysis?
17.Were point estimates and measures of variability presented for the primary outcome measures?
Table 3. Analysis of training stimulus
Aerobic exercise Resistive exercise
1. Intensity: 55 - 85% of maximum heart rate or 40 - 75% of
maximum heart rate reserve or 40 - 75% of maximum oxygen
uptake reserve;
2. Duration of sessions: 20 - 60 min (minimum of 10 min. con-
tinuous bouts throughout the day) or exercise to tolerance;
3. Frequency: at least three days per week; 4. Total exercise period:
at least six weeks
1. Intensity: 10-15 repetitions to near fatigue or at least 60% of
one Repetition Maximum;
2. Number of sets completed (duration): at least 1set;
3. Frequency: two or three days per week;
4. Total exercise period: at least six weeks.
Table 4. SMD/WMD calculation
Outcome Study-ID Instruments, units Calculation base
Cardiorespiratory Fitness Campbell 2005;
Drouin 2002;
Mock 1997;
Segal 2001 SD;
Segal 2001 SU
metres (12-minute walk);
peak VO2;
feet (12-minute walk);
peak VO2;
peak VO2
final values
Strength Drouin 2002 kg final values
Fatigue Campbell 2005;
Drouin 2002;
Mock 1997;
Mock 2004;
Segal 2001 SD;
Segal 2001 SU
Piper Fatigue Scale;
Piper Fatigue Scale;
Symptom Assessment Scale;
Piper Fatigue Scale;
SF-36 vitality reversed;
SF-36 vitality reversed;
final values
Weight change Mac Vicar 1989;
Segal 2001 SD;
Segal 2001 SU
kg change scores
Cancer specific quality of life Campbell 2005 Functional Assessment of Can-
cer Therapy - general (FACT-
G)
change scores
Cancer -site specific quality of
life
Campbell 2005 Functional Assessment of Can-
cer Therapy-Breast (FACT-B)
change scores
Anxiety Mock 1997 Symptom Assessment Scale final values
35Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 4. SMD/WMD calculation (Continued)
Mood Disturbance Drouin 2002 Profile of Mood States (POMS) final values
Depression Mock 1997 Symptom Assessment Scale final values
T-Cells Drouin 2002 CD4+/CD8+ final values
Natural Killer Cells Drouin 2002 Natural killer cytotoxic activity,
lytic units
final values
Oxidative Stress Drouin 2002 8-Isoprostane final values
Sleep disturbances Mock 1997 Symptom Assessment Scale final values
Table 5. Methodological Scores
Study Internal Validity Descriptive Validity Statistical Validity Total Score
Items Items Items
2, 3, 6, 7, 8, 9, 11, 14,
16; Score
1, 4, 5, 10, 12, 13; Score 15, 17; Score
Campbell 2005 +, ?, +, +, ?, +, +, +, -, 6 +, +, +, +, +, -, 5 +, +, 2 13
Crowley 2003 +, +, +, +, +, +, +, +, +, 9 +, -, -, +, +, -, 3 +, -, 1 13
Drouin 2002 +, +, ?, +, ?, +, +, +, -, 6 +, +, -, +, +, -, 4 +, +, 2 12
MacVicar 1986 -, ?, ?, ?, ?, +, +, +, ?, 3 +, ?, +, -, +, -, 3 +, -, 1 7
MacVicar/ Winningham
1989
?, ?, +, +, ?, +, -, +, -, 4 +, +, -, -, +, -, 3 +, -, 1 8
Mock 1997 -, -, +, +, ?, +, +, +, -, 5 +, +, +, +, +, -, 5 -, -, 0 10
Mock 2004 +, +, +, -, -, +, +, +, +, 7 +, +, +, +, +, -, 5 +, +, 2 14
Segal 2001 +, +, ?, +, ?, +, -, +, +, 6 +, +, +, +, +, -, 5 +, +, 2 13
Winningham 1988 ?, ?, +, ?, ?, +, +, +, +, 5 +, +, +, -, +, - , 4 +, -, 1 10
36Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A P P E N D I C E S
Appendix 1. Medline search strategy (1966-2004) (OVID)
1.RANDOMIZED-CONTROLLED-TRIAL in PT
2.CONTROLLED-CLINICAL-TRIAL in PT
3.RANDOMIZED-CONTROLLED-TRIALS
4.RANDOM-ALLOCATION
5.DOUBLE-BLIND-METHOD
6.SINGLE-BLIND-METHOD
7.#1 or #2 or #3 or #4 or #5 or #6
8.(TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
9.#7 not #8
10.CLINICAL-TRIAL in PT
11.explode CLINICAL-TRIALS/ all subheadings
12.(clin* near trial*) in TI
13.(clin* near trial*) in AB
14.(singl* or doubl* or trebl* or tripl*) near (blind* or mask*)
15.(#14 in TI) or (#14 in AB)
16.PLACEBOS
17.placebo* in TI
18.placebo* in AB
19.random* in TI
20.random* in AB
21.RESEARCH-DESIGN
22.#10 or #11 or #12 or 13 #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21
23.((TG=ANIMALS) not (TG=HUMAN)) and (TG=ANIMALS)
24.#22 not #23
25.#24 not #9
26.TG=COMPARATIVE-STUDY
27.explode EVALUATION-STUDIES/ all subheadings
28.FOLLOW-UP-STUDIES
29.PROSPECTIVE-STUDIES
30.control* or prospectiv* or volunteer*
31.(#30 in TI) or (#30 in AB)
32.#26 or #27 or #28 or #29 or #31
33.(TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
34.#32 not #33
35.#34 not (#9 or #25)
36.#9 or #25 or #35
37.explode “Breast-Neoplasms”/ all subheadings
38.Cancer*
39.Carcinom*
40.Neoplas*
41.Malignan*
42.#38 or #39 or #40 or #41
43.Breast*
44.#42 and #43
45.#37 or #44
46.explode “Exercise”/ all subheadings
47.explode “Exercise-Movement-Techniques”/ all subheadings
48.explode “Exercise-Therapy”/ all subheadings
49.explode “Physical-Education-and-Training”/ all subheadings
37Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
50.explode “Physical-Fitness”/ all subheadings
51.explode “Exertion”/ all subheadings
52.explode “Sports”/ all subheadings
53.(sport or sports) in ti, ab
54.physical activit* in ti,ab
55.kinesi?therap* in ti,ab
56.exercise* in ti, ab
57.walking in ti, ab
58.jogging in ti, ab
59.swimming in ti, ab
60.cycling in ti, ab
61.bicycling in ti, ab
62.weight in ti, ab
63.training in ti, ab
64.muscle in ti, ab
65.strengthening in ti, ab
66. endurance in ti, ab
67.#46 or #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or 57# or #58 or #59 or #60 or #61 or #62 or #63 or
#64 or #65 or #66
68.#36 and #45 and #67
W H A T ’ S N E W
Last assessed as up-to-date: 15 July 2004.
Date Event Description
9 September 2008 Amended Converted to new review format.
H I S T O R Y
Protocol first published: Issue 4, 2004
Review first published: Issue 4, 2006
C O N T R I B U T I O N S O F A U T H O R S
MM: electronic searching and handsearching, study selection, data extraction, methodological assessments, quantitative and qualitative
synthesis of included studies, reporting.
TB: study selection, data extraction, methodological assessments, quantitative and qualitative synthesis of included studies, manuscript
review.
KLR: contacted experts for identifying additional trials, contributed to consensus finding when disagreement in data extraction and
methodological assessments persisted between the other two authors (MM, TB), contacted trial investigators for additional data,
contributed to planning of quantitative synthesis of studies; reviewed manuscript.
38Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D E C L A R A T I O N S O F I N T E R E S T
None known
I N D E X T E R M SMedical Subject Headings (MeSH)
∗Exercise Therapy; Breast Neoplasms [∗therapy]; Chemotherapy, Adjuvant [adverse effects]; Fatigue [rehabilitation]; Physical Fitness;
Radiotherapy, Adjuvant [adverse effects]; Randomized Controlled Trials as Topic; Weight Gain
MeSH check words
Female; Humans
39Exercise for women receiving adjuvant therapy for breast cancer (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.