Fatigue in Long-Term Breast Carcinoma Survivors
A Longitudinal Investigation
Julienne E. Bower, Ph.D.1–3
Patricia A. Ganz, M.D.3–5
Katherine A. Desmond, M.S.6
Coen Bernaards, Ph.D.7
Julia H. Rowland, Ph.D.8
Beth E. Meyerowitz, Ph.D.9
Thomas R. Belin, Ph.D.2,3,10
1Cousins Center for Psychoneuroimmunology, Se-
mel Institute for Neuroscience, University of Cali-
fornia at Los Angeles, Los Angeles, California.
2Department of Psychiatry and Biobehavioral Sci-
ences, David Geffen School of Medicine, University of
California at Los Angeles, Los Angeles, California.
3Division of Cancer Prevention and Control Re-
search, Jonsson Comprehensive Cancer Center,
University of California at Los Angeles, Los Ange-
4Department of Medicine, David Geffen School of
Medicine, University of California at Los Angeles,
Los Angeles, California.
5Department of Health Services, School of Public
Health, University of California at Los Angeles, Los
6Statistical Consultant, Culver City, California.
7Oncology Biostatistics, Genentech, South San
8Office of Cancer Survivorship, Division of Cancer
Control and Population Sciences, National Cancer
Institute, Bethesda, Maryland.
9Department of Psychology, University of South-
ern California, Los Angeles, California.
10Department of Biostatistics, University of Cali-
fornia at Los Angeles, Los Angeles, California.
R01CA63028 from the National Cancer Institute.
Address for reprints: Julienne E. Bower, Ph.D., 300
UCLA Medical Plaza, Room 3306, Box 957076, Los
Angeles, CA 90095-7076; Fax: (310) 794-9247;
Dr. Bower was supported in part by career devel-
opment awards from the National Cancer Institute
(K07 CA90407) and the California Breast Cancer
Dr. Ganz was supported in part by an American
Cancer Society Clinical Research Professorship.
Received June 21 2005; revision received August
16 2005; accepted September 19 2005.
BACKGROUND. A longitudinal study was designed to evaluate the prevalence, per-
sistence, and predictors of posttreatment fatigue in breast carcinoma survivors.
METHODS. A sample of 763 breast carcinoma survivors completed questionnaires at
1–5 and 5–10 years after diagnosis, including the RAND 36-item Health Survey,
Center for Epidemiological Studies – Depression scale (CES-D), Breast Cancer
Prevention Trial Symptom Checklist, and demographic and treatment-related
RESULTS. Approximately 34% of study participants reported significant fatigue at
5–10 years after diagnosis, which is consistent with prevalence estimates obtained
at 1–5 years after diagnosis. Approximately 21% reported fatigue at both assess-
ment points, indicating a more persistent symptom profile. Longitudinal predic-
tors of fatigue included depression, cardiovascular problems, and type of treat-
ment received. Women treated with either radiation or chemotherapy alone
showed a small improvement in fatigue compared with those treated with both
radiation and chemotherapy.
CONCLUSIONS. Fatigue continues to be a problem for breast carcinoma survivors
many years after cancer diagnosis, with 21% reporting persistent problems with
fatigue. Several factors that may contribute to long-term fatigue are amenable to
intervention, including depression and comorbid medical conditions. Cancer
2006;106:751–8. © 2006 American Cancer Society.
KEYWORDS: breast carcinoma, cancer survivor, fatigue, quality of life.
inent among cancer patients undergoing treatment and may persist
for months or years after successful treatment completion. Indeed,
research conducted with breast carcinoma survivors has shown that
approximately 30% report significant fatigue within the first 5 years
after diagnosis.2–4However, to our knowledge, only a few studies to
date have examined fatigue in long-term cancer survivors (i.e., indi-
viduals who are more than 5 years postcancer diagnosis). As survival
times for women with early-stage breast carcinoma lengthen, under-
standing the long-term effects of cancer treatments on this central
aspect of women’s functioning has taken on increasing importance.
Early research on quality of life in breast carcinoma survivors up
to 10 years after diagnosis found that fatigue was the most commonly
reported symptom, providing initial evidence for the prevalence and
atigue is increasingly recognized as the most common and dis-
tressing side effect of cancer and its treatment.1Fatigue is prom-
© 2006 American Cancer Society
Published online 9 January 2006 in Wiley InterScience (www.interscience.wiley.com).
persistence of this problem.5,6In a more recent study,
breast carcinoma survivors assessed at 5–15 years after
diagnosis reported increased fatigue relative to a
matched control group with no cancer history.7Sim-
ilar results have been observed among long-term sur-
vivors of Hodgkin lymphoma and testicular carci-
noma, who report greater fatigue than population
controls.8–10Cella et al.11recently examined the prev-
alence of cancer-related fatigue in a U.S. sample of
mixed cancer survivors. Among patients who com-
pleted treatment more than 5 years before, 33% re-
ported at least 2 weeks of fatigue in the previous
month. It is interesting to note that none of these
studies found an association between time since can-
cer diagnosis/treatment and fatigue severity, suggest-
ing that fatigue may not improve even in the late
posttreatment period. However, conclusions regard-
ing the course of posttreatment fatigue are limited by
the cross-sectional nature of these reports.
Fatigue is a multidimensional condition that in-
volves subjective feelings of tiredness, weakness,
and/or lack of energy. The etiology of cancer-related
fatigue has not yet been determined, although tumor
and treatment-related factors, psychosocial factors,
physical symptoms, and medical conditions have
been proposed as potential contributors.12Studies
conducted with patients undergoing treatment and in
the first 5 years after treatment completion have iden-
tified depressed mood as one of the strongest corre-
lates of fatigue, although fatigue cannot be explained
entirely by depression.13Other correlates of fatigue
include pain, sleep disturbance, presence of medical
comorbid conditions, and age.2,14In contrast, disease-
and treatment-related factors are not found to be con-
sistently correlated with fatigue,14–16nor do biological
factors such as anemia fully account for fatigue symp-
tomatology.17The few studies of long-term survivors
conducted to date have yielded similar results; in par-
ticular, the one study to assess psychologic symptoms
found that depressed mood and anxiety were strongly
correlated with fatigue severity,9whereas none of the
studies found an association between type of treat-
ment and fatigue5,8–10or between hemoglobin and
fatigue.10Other factors that are known to be relevant
for cancer survivors, such as fear of cancer recurrence,
to our knowledge have not been examined in relation
The current study was designed to evaluate the
prevalence and persistence of fatigue in a large sample
of disease-free breast carcinoma survivors assessed
longitudinally at 1–5 and 5–10 years after diagnosis. In
an earlier investigation of this sample, we reported on
the prevalence and correlates of fatigue at the 1–5-year
assessment point.2Results showed that approximately
one-third of breast carcinoma survivors reported sig-
nificant fatigue, and that the primary correlates of
fatigue were depressed mood and pain. In contrast,
treatment-related factors were found to be only
weakly correlated with fatigue. The current study had
two primary goals: 1) to provide information regarding
the prevalence and persistence of fatigue in long-term
breast carcinoma survivors; and 2) to identify predic-
tors of fatigue at 5–10 years after diagnosis in an effort
to determine potential mechanisms for this symptom.
MATERIALS AND METHODS
Participants were initially recruited to participate in a
study examining health-related quality of life in the
first 5 years after breast carcinoma diagnosis. Recruit-
ment for this initial study was conducted between
September 1994 and June 1997 in Los Angeles and
Washington, DC. The sample included 1957 women
who had been diagnosed with early-stage breast car-
cinoma between 1–5 years earlier, were free of disease,
and had completed all cancer therapies other than
tamoxifen. Details regarding study recruitment proce-
dures have been provided in earlier publications.18,19
In 1998, we recontacted women from the initial
study who were at least 5 years postdiagnosis to par-
ticipate in a follow-up assessment. We sent each
woman an invitation letter that included a response
form and postage-paid return envelope. Respondents
who indicated an interest in participating were mailed
the study questionnaires with a postage-paid return
envelope. All questionnaires were reviewed for com-
pleteness and participants were contacted to obtain
missing data. Study procedures were approved by the
institutional review boards at the University of Cali-
fornia, Los Angeles, and at Georgetown University
School of Medicine. All subjects provided informed
Study participants completed standardized question-
naires assessing health-related quality of life, physical
symptoms, affect, social support, and psychologic re-
sponses to the cancer experience. A complete descrip-
tion of these outcomes is provided by Ganz et al.20The
current study focuses on the following measures.
The SF-36 contains eight individual subscales that
represent the three general areas of health-related
quality of life: physical, emotional, and social well-
being.21,22The two scales of interest in this study were
the vitality subscale and the bodily pain subscale,
which were completed at each assessment.
752CANCER February 15, 2006 / Volume 106 / Number 4
The vitality subscale of the SF-36 consists of 4
items assessing how much of the time the individual
“felt full of pep,” “had a lot of energy,” “felt worn out,”
and “felt tired” during the past 4 weeks. As with the
other subscales on this instrument, standardized
scores on the vitality subscale range from 0–100, with
higher scores indicating better functioning (i.e., higher
levels of energy). The vitality subscale is bipolar in
nature; scores above the midpoint of 50 represent
well-being whereas scores below 50 represent limita-
tions or disability related to fatigue. Thus, a score of
100 is only earned by individuals who report feeling
full of pep and energy all of the time, and a score of 0
is earned only by those who report feeling tired and
worn out all of the time. This scale has been used as
the principal validation measure for more detailed
fatigue inventories developed specifically for cancer
patients (e.g., Fatigue Symptom Inventory and Multi-
dimensional Fatigue Symptom Inventory) and there is
a high correlation between scores on these mea-
sures.23,24Indeed, breast carcinoma survivors who
score at or below 50 on the vitality scale demonstrate
alterations in biologic and psychologic/behavioral
processes relative to survivors who score above 50,
supporting the validity of this cut-point.2,25–28
The bodily pain subscale of the SF-36 includes 2
items that assess the severity of bodily pain and the
extent to which pain interfered with daily activities
over the past 4 weeks. Higher scores on this measure
indicate lower levels of pain and pain-related disrup-
tion. Scores range from 0–100.
Center for Epidemiologic Studies – Depression Scale
This 20-item self-report questionnaire was designed to
assess depressive symptomatology in the general pop-
ulation.29Respondents indicate how often they have
experienced a variety of symptoms during the past
week on a four-point scale ranging from “rarely or
none of the time” to “most or all of the time.” Higher
scores on this measure indicate higher levels of de-
pressive symptomatology, with scores equal to or
greater than 16 indicating an increased risk of clinical
depression. Scores range from 0–60. This measure
was completed at each assessment point.
Breast Cancer Prevention Trial (BCPT) Symptom Checklist
This 43-item list of commonly reported physical and
psychologic symptoms was developed specifically for
the BCPT30. Respondents indicate how much they
have been bothered by each symptom in the past 4
weeks on a 4-point scale ranging from “not at all” to
“extremely.” For this study, we used only those items
that assessed vasomotor symptoms (hot flashes, night
sweats) based on research showing an association be-
tween menopausal symptoms and fatigue in breast
carcinoma survivors.15Because of skewed distribu-
tions, responses to these items were grouped and
coded categorically (present/not present). The BCPT
symptom checklist was completed at each assessment
Fear of Recurrence Scale
A modified version of the Fear of Recurrence Scale was
administered at the follow-up assessment.31This six-
item scale assesses worries about cancer recurrence
and regarding one’s future health status. Respondents
indicate how much they agree with each statement on
a five-point scale ranging from “strongly disagree” to
“strongly agree.” Scores range from 0–5, with higher
scores indicating greater fear and uncertainty con-
cerning the possibility of cancer returning.
Demographic and medical data
Information regarding demographics, medical condi-
tions, and breast carcinoma treatment was obtained
by self-report at the initial assessment and updated at
Our analytic approach proceeded in several steps.
First, we identified a group of women who scored in
the fatigued range on the SF-36 vitality subscale (i.e.,
scored at or below the scale midpoint of 50) at the
follow-up assessment. Second, we compared these
women with women who scored above 50 at the fol-
low-up assessment on selected demographic, treat-
ment-related, and psychosocial variables and con-
ducted logistic regression
predictors of fatigue status at Time 2. Third, we con-
ducted logistic regression analyses to identify longitu-
dinal predictors of fatigue status using baseline values
of predictor variables. We also conducted ordinary
least-squares multiple regression analyses to identify
concurrent and longitudinal predictors of fatigue us-
ing continuous scores on the SF-36 vitality scale as the
Standard statistical tests were performed for con-
tinuous and categoric variables, including Pearson
product-moment correlation to calculate associations
among continuous variables, ?2tests to calculate as-
sociations among categorical variables, Student t tests
to compare means of continuous variables for two
groups and one-way analysis of variance to compare
means of continuous variables for three or more
groups. Logistic regression was used to evaluate the
effect of selected predictor variables on the likelihood
of being fatigued, and multiple regression was used to
Fatigue in Long-Term Breast CA Survivors/Bower et al. 753
evaluate the effect of selected predictor variables on
level of fatigue.
Recruitment Results and Characteristics of Participants
A total of 1336 subjects met the study eligibility criteria
(i.e., were at least 5 years postdiagnosis) and were sent
recruitment letters. Response forms were received
from 1063 participants: 914 (86%) indicated that they
were interested in participating, 79 (7%) were not in-
terested, 58 (5%) could not be located, and 12 (1%)
were deceased. Questionnaires were sent to the 914
interested respondents: 817 (89%) returned the ques-
tionnaires, 22 (2%) explicitly refused, and 75 (8%)
failed to return the booklet despite reminder calls.
Overall, completed questionnaires were received from
61% of the 1336 survivors initially contacted.
We compared women who participated in the fol-
low-up study (n ? 817) with women who either did
not respond to the invitation letter or did not return
the study questionnaires (n ? 519). Student t tests
indicated that study participants reported significantly
higher levels of vitality (mean, 61.1) compared with
nonparticipants (mean, 58.5; P ? 0.03), although the
absolute difference was not larger (2.6-point differ-
ence). Participants were also better educated, more
likely to be white, were less depressed, and scored
higher on several measures of quality of life than non-
participants. There were no differences in type of can-
cer treatment received. Further details of recruitment
results and characteristics of responders and nonre-
sponders are provided elsewhere.20
Of the 817 respondents, 54 reported a breast car-
cinoma recurrence and were not included in the cur-
rent study given our focus on fatigue in disease-free
survivors.20,32Therefore, the final sample was com-
prised of 763 disease-free survivors. The average time
between the initial (Time 1) and follow-up (Time 2)
assessments was 2.8 years (range, 1–4 yrs).
Prevalence of Fatigue
As reported by Ganz et al.,20there was no change in
mean vitality scores noted from Time 1 (mean, 61.4;
standard deviation [SD] of 20.4) to Time 2 (mean, 60.9;
SD of 20.9). A similar percentage of women scored in
the ‘fatigued’ range of the vitality scale at each assess-
ment point. In our initial examination of fatigue at 1–5
years after diagnosis, 35% of the women were classi-
fied as fatigued; at the 5–10-year follow-up, 34% were
classified as fatigued.
In addition to determining the point prevalence of
fatigue at each assessment, a primary goal of this
study was to evaluate the persistence of fatigue over
time. Among women classified as fatigued at Time 1,
63% (n ? 160) continued to score in the fatigued range
of the vitality scale at Time 2. Among women classified
as nonfatigued at Time 1, 81% (n ? 409) continued to
score in the nonfatigued range at Time 2. When cal-
culated as a percentage of the total sample, 21% of
study participants scored in the fatigued range at each
assessment point, 54% scored in the nonfatigued
range at each assessment point, 12% scored in the
fatigued range at baseline and in the nonfatigued
range at follow-up, and 13% scored in the nonfatigued
range at baseline and in the fatigued range at follow-
Concurrent Predictors of Fatigue
To probe factors that may underlie fatigue in long-
term survivors, we first compared women who scored
in the fatigued range of the SF-36 vitality scale at Time
2 (mean vitality score, 36.8; SD of 12.1) with those who
scored in the nonfatigued range at Time 2 (mean
vitality score, 73.2; SD of 11.6) on selected variables
(Table 1). Several demographic variables were as-
sessed, including age, income, and marital status,
each of which was associated with fatigue in our initial
report.2Only income was associated with fatigue
group at follow-up, with fatigued women reporting
lower income than nonfatigued women (P ? 0.05). We
also examined the association between fatigue and
several medical conditions that may influence fatigue
levels, including diabetes, high blood pressure, heart
problems, and arthritis. All of these conditions were
more prevalent among fatigued women than nonfa-
tigued women. Psychologic and physical symptoms
were found to be strongly associated with fatigue, a
finding that was consistent with our initial report.
Fatigued women reported significantly higher levels of
depressive symptoms, more bodily pain (as indicated
by lower scores on the SF-36 pain scale), and more hot
flashes and night sweats than nonfatigued women.
Fear of cancer recurrence was also significantly higher
in the fatigued group. In terms of treatment-related
factors, the results demonstrated that type of cancer
treatment was significantly associated with fatigue
group at follow-up. This difference appeared to be
driven by two treatment groups: radiation alone, and
radiation and chemotherapy. Fatigued women were
less likely to have been treated with radiation alone
than nonfatigued women, and were more likely to
have been treated with a combination of radiation and
chemotherapy. The use of tamoxifen and time since
diagnosis were not found to be significantly associated
with fatigue group.
A logistic regression analysis was conducted in-
cluding predictor variables that were significantly as-
754CANCER February 15, 2006 / Volume 106 / Number 4
sociated with fatigue in the bivariate analyses (i.e.,
income, medical conditions, depressive symptoms,
bodily pain, hot flashes/night sweats, fear of recur-
rence, and type of cancer treatment). All of the pre-
dictors, with the exception of treatment type, were
measured at follow-up. The model including all ex-
planatory variables was significant (P ? 0.0001). As
shown in Table 2, depressive symptoms, pain, and
high blood pressure were all found to be significant
predictors of being fatigued at 5–10 years after diag-
nosis. Treatment category was found to be a margin-
ally significant predictor (P ? 0.08 for overall treat-
ment group). Follow-up
demonstrated that women treated with both radiation
and chemotherapy were more likely to be fatigued
than women treated with radiation alone (P ? 0.016),
which is consistent with bivariate results. Income was
not significant in the regression model. These results
are largely consistent with logistic regression analyses
conducted at Time 1 in the full sample of study par-
ticipants (n ? 1927). As reported by Bower et al.,2
depression, pain, and high blood pressure were signif-
icant cross-sectional predictors of fatigue at Time 1, as
were arthritis and age; however, treatment category
was not found to be a significant predictor at this
Multiple regression analyses also were conducted
to evaluate the association between predictor vari-
ables and level of fatigue at the follow-up assessment.
Results were largely consistent with logistic regres-
sion; depressive symptoms and pain were found to be
significant predictors of fatigue, as was treatment with
radiation and chemotherapy (compared with radia-
tion alone). In the multiple regression model, heart
disease was found to be a significant predictor of
fatigue (P ? 0.049), and high blood pressure was mar-
ginally significant (P ? 0.097). Overall, the predictor
variables explained 45% of the variance in fatigue
scores at followup (R2? 0.45; P ? 0.0001).
Longitudinal Predictors of Fatigue
In addition to examining concurrent predictors of fa-
tigue, a primary goal of the current study was to iden-
tify longitudinal predictors of fatigue. Logistic regres-
sion analyses were conducted including variables that
were significant predictors of fatigue in logistic regres-
sion models conducted at either Time 1 (identified in
Characteristics of Fatigued and Nonfatigued Survivors at Follow-Up
(n ? 257)
(n ? 504)Pa
Mean age in yrs (SD)
High blood pressure
CES-D depression, mean (SD)
SF-36 bodily pain, mean (SD)
Hot flashes/night sweats
Fear of recurrence, mean (SD)
Type of cancer treatment
Radiation and chemotherapy
Use of tamoxifen
Mean yrs since diagnosis, (SD)
58.8 (11.5) 59.0 (10.3)0.86
SD: standard deviation; CES-D: Center for Epidemiological Studies – Depression scale.
aP values were derived from Student t tests for continuous variables and ?2for categoric variables.
Percentages are based on available data and may not add up to 100 due to rounding.
Multivariate Logistic Regression with Concurrent Predictors of
Fatigue Status at Follow-Up
Follow-up predictor variable OR 95% CI
High blood pressure
SF-36 bodily paind
Hot flashes/night sweats
Fear of cancer recurrence
Type of cancer treatmente
OR: odds ratio; 95% CI: 95% confidence interval; CES-D: Center for Epidemiological Studies – Depres-
aComparison group is income ? $100,000.
bP ? 0.05.
cP ? 0.0001.
dHigher scores indicate less pain.
eComparison group is radiation and chemotherapy.
Fatigue in Long-Term Breast CA Survivors/Bower et al. 755
Bower et al.2) or Time 2. These included age, income,
menopausal symptoms, and type of treatment re-
ceived, all measured at baseline. Baseline fatigue score
was also included as a predictor.
The results are shown in Table 3. As expected,
baseline fatigue score was a strong predictor of fatigue
group at follow-up; women who reported higher levels
of fatigue at 1–5 years after diagnosis were signifi-
cantly more likely to be fatigued at 5–10 years after
diagnosis. In addition, women who reported higher
levels of depressive symptoms and who had high
blood pressure at baseline were significantly more
likely to be fatigued at follow-up. Bodily pain was a
marginal predictor of fatigue group. The overall test
for treatment category was significant (P ? 0.04). Pair-
wise comparisons of the treatment groups indicated
that women treated with radiation and chemotherapy
were more likely to be fatigued than women treated
with radiation alone (P ? 0.005) or chemotherapy
alone (P ? 0.04).
Multiple regression analyses with continuous scores
on the SF-36 vitality scale as the outcome variable
showed a similar pattern of results. Baseline fatigue,
depression, and bodily pain were all found to be signif-
icant predictors of fatigue severity at follow-up, as was
type of cancer treatment received. Consistent with the
concurrent multiple regression model, heart disease was
found to be a significant predictor of fatigue and high
blood pressure was not. Overall, baseline predictor vari-
ables accounted for 46% of the variance in follow-up
fatigue scores (R2? 0.46; P ? 0.0001).
To our knowledge, the current study is the first large-
scale, longitudinal study of fatigue symptoms in long-
term breast carcinoma survivors. At 5–10 years after di-
agnosis, 34% of the women surveyed reported elevated
fatigue as indicated by scores on the SF-36 vitality scale.
The prevalence of fatigue at this assessment point was
nearly identical to that observed at 1–5 years after diag-
tom over time.20These prevalence estimates are similar
to those seen in studies conducted with breast carci-
noma survivors in the first years after diagnosis3,4and
with longer-term survivors. For example, Cella et al.11
found that 33% of cancer survivors who had completed
treatment more than 5 years previously had experienced
a 2-week period of fatigue in the month before assess-
ies demonstrating no association between time since
diagnosis and fatigue.8–10
The current study results also provide information
regarding the prevalence of persistent fatigue in breast
carcinoma survivors. Approximately 21% of the
women surveyed reported fatigue at both assessment
points, suggesting a more enduring problem. Interest-
ingly, a similar percentage (20%) of the long-term
survivors assessed by Cella et al.11reported that they
had not only experienced a 2-week period of fatigue,
but that the fatigue had caused significant disruption
in their daily activities. It is possible that, whereas
one-third of survivors report fatigue at any given time,
a smaller group of patients may experience more per-
sistent and/or debilitating fatigue symptoms that lead
to impairment in functioning. There was also evidence
for fluctuations in fatigue status; approximately 25% of
study participants moved from 1 fatigue group to the
other over the course of the follow-up period. To date,
there is little information available regarding the tem-
poral pattern of fatigue in cancer survivors; it is un-
clear whether this symptom waxes and wanes, with
some periods of increased energy, or is relatively con-
stant from day to day. Descriptive accounts highlight
the pervasiveness of cancer-related fatigue,33but em-
piric research is lacking. Longitudinal studies involv-
ing repeated assessment of fatigue in survivor popu-
lations are required to address this important issue.
A second goal of the current study was to identify
Multivariate Logistic Regression with Longitudinal Predictors of
Fatigue Status at Follow-Up
Baseline predictor variableOR 95% CI
? 50 yrs
High blood pressure
SF-36 bodily paing
Hot flashes/night sweats
Type of cancer treatmenth
OR: odds ratio; 95% CI: 95% confidence interval; SF-36: ; CES-D: Center for Epidemiological Studies –
aHigher scores indicate more vitality/less fatigue.
bP ? 0.0001.
cComparison group is age over 60 years.
dComparison group is income over $100,000.
eP ? 0.05.
fP ? 0.01.
gHigher scores indicate less pain.
hComparison group is radiation and chemotherapy.
756CANCER February 15, 2006 / Volume 106 / Number 4
predictors of long-term fatigue. Analyses conducted in
the full sample highlighted two factors associated with
fatigue in breast carcinoma survivors: cardiovascular
problems and presence of depressive symptoms.
Cross-sectional studies support an association be-
tween comorbid medical conditions and fatigue in
cancer survivors, including cardiovascular disorders.9
The results of the current study extend these findings
by demonstrating that breast carcinoma survivors
with high blood pressure or heart disease face an
increased risk of fatigue in the 5–10 years after diag-
nosis. The majority of women who reported high
blood pressure also reported use of antihypertensive
medications, which are associated with fatigue in non-
cancer populations.34These findings suggest that at-
tention to comorbid medical conditions and related
medications are an important part of caring for the
Fatigue is known to co-occur with depression in
cancer patients and survivors,13although the lack of
longitudinal research has complicated the interpretation
of these results. In particular, it is unclear whether de-
pression predicts changes in fatigue over time, which
might suggest that depression underlies or perpetuates
fatigue symptoms. A recent longitudinal study con-
ducted with breast carcinoma patients undergoing radi-
ation therapy found that depressed mood before treat-
ment was associated with increased fatigue 2.5 years
later, although pretreatment fatigue levels were not con-
trolled in this report.35The current study results indicate
first years after diagnosis are at increased risk for long-
term fatigue, even after controlling for initial fatigue
scores. Overall, the results of the current study confirm
the close links between fatigue and depression and high-
light the importance of carefully assessing depression in
cancer survivors who report problems with fatigue.
The third predictor of long-term fatigue in this sam-
ple was the type of cancer treatment received. Previous
studies have not found a strong association between
cancer treatments and fatigue in long-term survivors of
Hodgkin disease or testicular carcinoma.8–10The few
studies to evaluate treatment effects in breast carcinoma
survivors have yielded similar results,10,14including our
initial examination of this patient cohort at 1–5 years
after diagnosis.2The current results suggest that the ef-
fects of cancer treatments may be most apparent in
longer-term breast carcinoma survivors. In particular,
women treated with either radiation or chemotherapy
showed a small improvement in fatigue at 5–10 years
after diagnosis compared with those treated with both
radiation and chemotherapy. It is possible that some of
the fatigue experienced at the initial assessment point
was related to these cancer treatments and resolved over
a longer follow-up period. The lack of recovery among
women treated with radiation and chemotherapy is con-
sistent with results from the parent study, which found
detrimental effects of adjuvant therapy among long-
term survivors,20and suggests that more aggressive
treatments may have long-term, subtle effects on quality
The current study has several limitations that merit
attention. First, the study focused on women in 2 large
urban areas and yielded a response rate of 61% at the
follow-up assessment, which may have biased results.
Furthermore, participants in the follow-up study scored
several points higher on the SF-36 vitality scale than
nonparticipants at the baseline assessment, suggesting
that the most fatigued women may have been underrep-
resented in our sample. It is noteworthy that our esti-
mates of fatigue prevalence are quite similar to those
obtained by Cella et al.,11who recruited cancer survivors
from a representative sample of 575,000 households
across the U.S. In addition, the predictors of fatigue
identified in this report (e.g., depressed mood) are con-
sistent with those found in previous research with can-
cer survivors,9supporting the validity of the current re-
sults.Second, because participants
assessed after cancer diagnosis and treatment, we can-
not determine whether their fatigue was specifically re-
lated to cancer. It is possible that fatigue is a stable
characteristic of certain individuals that has little to do
with the cancer experience. Previous studies have shown
elevated fatigue levels in breast carcinoma survivors rel-
ative to healthy controls,36,37suggesting that fatigue is
driven at least in part by aspects of the cancer experi-
ence. The current results also support cancer-specific
factors (i.e., type of cancer treatment) as contributors to
long-term fatigue. Prospective studies that assess
women before treatment onset and include a healthy
comparison group are needed to determine whether
fatigue is linked to cancer diagnosis and treatment, and
to identify unique and common predictors of fatigue in
cancer survivors and healthy women. A third limitation
of this study is the brief measure of fatigue, which pro-
vides information regarding fatigue frequency but does
not assess intensity, interference, or dimensions of fa-
tigue. Although this scale is highly correlated with more
comprehensive fatigue inventories,23,24use of these
measures in future studies should provide a more in-
depth portrait of cancer-related fatigue.
Overall, the findings of the current study highlight
the resilience of breast carcinoma survivors and sug-
gest that persistent fatigue is experienced by a minor-
ity of women in the aftermath of cancer diagnosis and
treatment. Further, they offer some hope that im-
provements in fatigue may be possible even up to 10
years after diagnosis and identify potential targets for
intervention, including depression and other comor-
bid medical conditions.
Fatigue in Long-Term Breast CA Survivors/Bower et al. 757
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