the experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative...

126 Journal of Pain and Symptom Management Vol. 34 No. 2 August 2007

Original Article

The Experience of Cancer-Related Fatigueand Chronic Fatigue Syndrome: A Qualitativeand Comparative StudyBarbara Bennett, RN, BSc, PhD, David Goldstein, MBBS, FRACP,Michael Friedlander, MD, PhD, Ian Hickie, AM, MBBS, MD, FRANZCP, andAndrew Lloyd, AM, MBBS, MD, FRACPDepartment of Medical Oncology (B.B., D.G., M.F.), Prince of Wales Hospital, Sydney, Australia, The

Brain and Mind Research Institute (I.H.), University of Sydney, Australia, and the School of Medical

Sciences (A.L.), University of New South Wales, Sydney Australia

AbstractCancer-related fatigue (CRF) is a common and disabling symptom complex reported bysurvivors. This study aimed to better understand the manifestations of CRF in womentreated for breast cancer, and to compare them with those of women diagnosed with chronicfatigue syndrome (CFS). Women with CRF persisting 6 months after treatment for early stagebreast cancer, and women with CFS participated in separate, audiotaped focus groups.Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted usinggrounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysisof transcripts from both groups revealed a similar core set of symptoms, featuring fatigue,neurocognitive difficulties, and mood disturbances. Women with CFS reported additionalsymptoms including musculoskeletal pain and influenza-like manifestations. Both groupssuffered disabling behavioral consequences of the symptom complex. Qualitatively, CRFappears closely related to CFS. These findings raise the emergent hypothesis of a conservedneurobehavioral symptom complex, which results from diverse triggering insults. J PainSymptom Manage 2007;34:126e135. � 2007 U.S. Cancer Pain Relief Committee.Published by Elsevier Inc. All rights reserved.

Key WordsCancer-related fatigue, chronic fatigue syndrome, fatigue, neurocognitive disturbance, mooddisorder, sleep disorder

Funding for this study was provided by the Depart-ment of Medical Oncology, Prince of Wales Hospitaland a Dissertation Grant (DISS 010353) from theSusan G. Komen Breast Cancer Foundation to thefirst author.

All authors declare that there is no actual or poten-tial conflict of interest which could inappropriatelyinfluence this work.

� 2007 U.S. Cancer Pain Relief CommitteePublished by Elsevier Inc. All rights reserved.

Address reprint requests to: Barbara Bennett, RN, BSc,PhD, Department of Medical Oncology, Prince ofWales Hospital, Randwick, NSW 2031, Australia.E-mail: [email protected]

Accepted for publication: October 23, 2006.

0885-3924/07/$esee front matterdoi:10.1016/j.jpainsymman.2006.10.014

mailto:[email protected]

Vol. 34 No. 2 August 2007 127The Experience of Cancer-Related Fatigue

BackgroundThe combination of surgery and adjuvant

treatment for early stage breast cancer is asso-ciated with a 90%e95% cure rate.1 Cross-sec-tional studies consistently record a highprevalence of prolonged fatigue often persist-ing many years after successful treatment forcancer.2e4 Recent prospective studies in bothtesticular cancer and Hodgkin’s disease survi-vors also identified high rates of fatigue lastingmonths to years after treatment.5e7 Such fa-tigue syndromes are under-recognized by phy-sicians and under-reported by patients.8,9

Cancer-related fatigue (CRF) has been pro-posed as a separate diagnostic entity in theInternational Classification of Diseases 10thRevision-Clinical Modification.10 These criteriaemphasize the complaint of fatigue, accom-panied by reported disturbances in cognitiveperformance and sleep, as well as loss ofmotivation. These manifestations should becausing functional impairment and be unex-plained by comorbid psychological disorder(see Table 1). These components are very sim-ilar to the diagnostic criteria for the more prev-alent disorder, chronic fatigue syndrome(CFS).11 As CFS commonly follows from acuteinfections such as glandular fever,12 the crite-ria also emphasize occurrence of additionalsymptoms including sore throat, headaches,and joint pain.

The focus group methodology is commonlyused to assist in developing a systematic recordof poorly characterized illnesses in health

sciences research.13 The facilitated interactionbetween participants with shared experiencesis a key component.14 This study describesthe characteristics of the unexplained fatiguestate following successful treatment for earlystage breast cancer (termed here postcancerfatigue [PCF]), and compared those character-istics with those of women diagnosed with CFS.The findings raise the suggestion that both fa-tigue states represent relatively stereotypedmanifestations of the host response to a trau-matic insult.

MethodThe sampling method for this focus group

study was systematic nonprobability (i.e., pur-posive) sampling15 with subjects chosen be-cause they reported the phenomenon underinvestigationda prolonged and unexplainedfatigue syndrome. Women were screened forprolonged fatigue using the SPHERE ques-tionnaire,16 which assesses a wide range of so-matic and psychological symptoms commonlyreported in medical and psychiatric settings.Reliability and construct validity of the instru-ment in identification of prolonged fatiguestates have been demonstrated,17 includingin women following adjuvant treatment forbreast cancer.18

Twenty-four consecutive women, who at-tended outpatient clinics in the Departmentof Medical Oncology at the Prince of WalesHospital, Sydney, Australia and who reportedprolonged fatigue after completing treatment

Table 1Diagnostic Criteria for CRF10

A. Six (or more) of the following symptoms have been present every day or nearly every day during the same two-week period inthe past month, and at least one of the symptoms is significant fatigue.� Significant fatigue, diminished energy, or increased need to rest, disproportionate to any recent change in activity level� Complaints of generalized weakness or limb heaviness� Diminished concentration or attention� Decreased motivation or interest to engage in usual activities� Insomnia or hypersomnia� Experience of sleep as unrefreshing or nonrestorative� Perceived need to struggle to overcome inactivity� Marked emotional reactivity (e.g., sadness, frustration, or irritability) to feeling fatigued� Difficulty completing daily tasks attributed to feeling fatigued� Perceived problems with short-term memory� Postexertional malaise lasting several hours

B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas offunctioning.

C. There is evidence from the history, physical examination, or laboratory findings that the symptoms are a consequence ofcancer or cancer therapy.

D. The symptoms are not primarily a consequence of comorbid psychiatric disorders such as major depression, somatizationdisorder, somatoform disorder, or delirium.

128 Vol. 34 No. 2 August 2007Bennett et al.

for cancer were approached. For inclusion,these women were required to meet study cri-teria for PCF, that is, the symptom complexmet the diagnostic criteria for CRF,10 and thesymptom complex had been present for atleast six months after completion of adjuvanttreatment for early stage breast cancer (i.e.,Stage I or II). Women were excluded if theirtreating oncologist indicated that they had ev-idence of significant comorbid medical (e.g.,anemia, cardiac, or endocrine disease) or psy-chiatric (e.g., psychotic disorder, substanceabuse) conditions that could explain the fa-tigue state.

A comparison group of 20 women with CFSwas approached, from the practices of two spe-cialist physicians in the same hospitaldone ininfectious diseases and one in immunology.Women were included if they had received a di-agnosis of CFS in accordance with the interna-tional diagnostic criteria.11

Women were excluded if they were unableto converse fluently in English. The institu-tional ethics committee approved the study,and written informed consent was obtainedfrom all subjects before participation.

Focus GroupsWomen with PCF and CFS participated in

separate focus groups. Each woman partici-pated in one focus group with three to six par-ticipants. Authors (BB and DG) acted asfacilitators. The predetermined frameworkfor the sessions was based on a series of brief,open-ended questions relating to symptomsand their consequences. After introductionsand outline of the purpose of the group, theopening question (aimed at identifying illnesscharacteristics that participants had in com-mon) was ‘‘Describe any problems or symptomsyou have had since finishing treatment.’’ (or‘‘since the onset of illness.’’ for women withCFS). Then followed questions seeking to en-courage participants to interact and discusstheir experiences. For example: ‘‘Would you ex-plain to me what it (the symptom) meant foryou?’’ or (to encourage participation) ‘‘Couldyou explain what your own experiences have beenlike?’’ The sessions were continued until nonew information was obtaineddthat is, to ‘‘sat-uration.’’ The session was closed with a sum-mary question by the moderator such as‘‘Have we missed anything?’’

All sessions were recorded on audiotape.The focus groups were conducted in a relaxedatmosphere (e.g., refreshments were pro-vided) and participation ‘‘ground rules’’ werestated at the outset, emphasizing that therewere no right or wrong answers, and highlight-ing privacy and confidentiality. The data col-lection process was interactive in thatinformation gleaned from one focus groupwas used to inform the process for the subse-quent group within the two diagnostic cate-gories (i.e., PCF and CFS).

Following each session, tapes were tran-scribed verbatim. All identifying characteristicswere removed from transcripts and fictitiousnames substituted.

Data AnalysisAn approach consistent with the grounded

theory tradition19 was chosen for the analysis.13

Grounded theory research seeks to producerich descriptions and theoretical explanationsof the phenomenon under investigation. Anal-ysis commenced as soon as possible after eachgroup was completed. Transcripts were im-ported into the NUD*IST software program(Non-numerical Unstructured Data Indexing,Searching, and Theorising),20 which facilitatesthe organization and analysis of qualitativedata.

The coding and categorization were per-formed by BB. At each stage of the analysis,the coding schema was developed by consulta-tion and discussion with an experienced oncol-ogist (DG) and a highly experienced clinicalresearcher in relation to fatigue syndromes(AL).

Data analysis was a multistage process. Firstlevel of analysis, coding of symptom concepts, en-tailed a thorough word-by-word, line-by-line ex-amination of transcripts to identify and labelthe experiences described. It was aimed at cap-turing each woman’s own meaning, and gener-ated a large number of preliminary concepts.This process also involved continued compari-sons when identifying, clarifying, and differen-tiating the concepts. Initial data reduction wasachieved by grouping together very closely re-lated descriptions of individual symptoms pro-vided by subjects within each session. Secondlevel of analysis required interpretation of thedata. Preset classification schemes wereavoided. Clusters of coded symptom concepts,


very similar in meaning or which consistentlyco-occurred, were categorized into more ab-stract level notions. Additionally, elements de-scribing symptoms were separated from thebehavioral consequences of the symptom orsymptom cluster. Categories were then linkedbased on their properties. For the third levelof analysis, axial coding, data were repeatedlyand exhaustively reexamined and comparedto ensure that no concepts had been omittedand no categories overlooked or inappropri-ately merged (i.e., that saturation had beenreached). The aim of axial coding was to in-form a model of the symptom paradigm foreach illness.

ResultsFocus Groups

Sixteen of 24 eligible women with PCF(67%) agreed to participate. Twenty womenwith CFS11 were approached and 12 agreedto participate (60%). The women who refusedor were unable to participate predominantlydid so because they reported that they were‘‘too fatigued’’ to travel to the hospital. Womenwho were approached but did not participatedid not differ significantly in age or illnesscharacteristics (data not shown). A total ofseven groups (three PCF and four CFS), eachcomprising three to six women, were con-ducted, with each session lasting 60e90 min-utes. The characteristics of the women inboth groups are displayed in Table 2. Women

Table 2Characteristics of the Women with Prolonged

Fatigue Participating in the Focus Groups

Subject Groups

Illness characteristics PCF (n¼ 16) CFS (n¼ 12)

Mean age (years) (range) 56 (43e71) 44 (31e67)a

Time posttreatment (CRF)or time since diagnosis(CFS) (months)

21 (6e48) 88 (30e500)b

Breast cancer treatmentMastectomy, % (n) 63 (10)Lumpectomy, % (n) 37 (6)Chemotherapy, % (n)c 100 (16)Radiotherapy, % (n) 69 (11)Tamoxifen, % (n) 50 (8)

aP¼ 0.005.bP¼ 0.05.cIncludes women who received combined chemotherapy andradiotherapy.

with CFS were younger (P¼ 0.005) than thosewith PCF, and had, on average, been symptom-atic longer (88 months vs. 21 months,P¼ 0.05).

Analysis of TranscriptsdPCF GroupsWhere possible, the women’s own words

were used initially to label the phenomenonor symptom being described. For the purposesof analysis and presentation, these descriptionswere uniformly modified to the present tense:‘‘I am very tired’’; ‘‘my brain’s gone’’; ‘‘I have no en-ergy.’’; ‘‘.now I’m lost for the word.’’ In this pre-liminary round, 86 symptoms relating to theexperience of PCF were identified. Where syn-onyms or very closely related symptoms weredescribed, these were grouped together andidentified as describing the same symptomdfor example, ‘‘I lose concentration.,’’ ‘‘I seemmore absent-minded,’’ and ‘‘I can’t fully concentrateon anything.’’

These 86 coded symptoms were sorted intofour categories that were supported followingcontinued reexamination of the data. The cat-egories identified (see Fig. 1) were 1) fatigue,which included ‘‘abnormal tiredness’’ implyingexaggerated fatigue after activity; ‘‘lack of en-ergy’’ implying fatigue at rest; and ‘‘unrefresh-ing sleep’’ describing the sense of awakeningfrom sleep without renewed energy; 2) neuro-cognitive impairment, including difficulties with‘‘memory,’’ particularly short-term memory;and ‘‘attention,’’ notably inability to sustainmental activity; and with ‘‘verbal fluency’’ in-cluding a sense of increased hesitancy in find-ing the words and sometimes feeling ‘‘lost forthe word’’; 3) mood disturbance components, in-cluding feelings of ‘‘sadness,’’ ‘‘frustration,’’and ‘‘worry’’; and 4) the final category in-cluded ‘‘miscellaneous symptoms’’dfor instance,those associated with menopause such as hotflushes, or (as one woman reported) the onsetof classical migraine headaches.

The behavioral impact of the symptoms wasidentified as a second categorization schemadthese fell into three domains including 1) phys-ical: ‘‘I can only do a handful of things - I knowI used to be able to do.,’’ ‘‘.I used to jump fences.I can’t jump fences any more.’’; 2) psychological:‘‘worrying that something had gone wrong’’ (i.e.,that the disease had progressed or that thetreatment had not been effective), ‘‘I am totallyin fear the whole time,’’ and ‘‘I feel this need to


Fatigue

Abnormal tiredness: “I get tired much earlier than usual”

Lack of energy:“… and I have no energy…”

Unrefreshing sleep: “I wake up and think – I’ve got

nothing out of this sleep at all…”

Neurocognitive

impairment

Word-finding difficulties:“…I’m lost for the word…”

Concentration problems: “I start reading and my mind

wanders”

Memory difficulties

Impact of the

fatigue state

Psychological

consequences

Emotional:“I’ve lost my confidence”

Behavioral:“I can’t even read a newspaper -

I’ve not read a paper in two years”

Physical consequences

Inability to function at work:

“At work I have to force myself

to stay awake. “

Inability to function at home:“I can only do a handful of things

I know I used to be able to do”

Mood disturbance

Low mood: “I’ve started feeling sorry for

myself”

Frustration:“I get really upset…”

Anxiety:“I am worried that something else

has gone wrong”

Social consequences

Workplace:“I’ve been an actress almost all my life

& now I’m too afraid to work because

of the memory loss and fatigue”

Home:“I fall asleep on the lounge…”

Fig. 1. Characteristics of PCFdanalysis of focus group transcripts.

cry..’’ These descriptions also included morepervasive manifestations, suggesting underly-ing anhedonia such as ‘‘.I think I can’t be both-ered doing it. I have no inspiration to do that atall.,’’ ‘‘You just lose interest’’; and 3) social con-sequences, such as ‘‘I feel I can only cope with go-ing to work and not doing all the other things that Idid before,’’ ‘‘I can’t even read a newspaper. I’ve notread a newspaper in two years..’’ All women withPCF reported that the prolonged course of ill-ness was a totally unexpected occurrence ‘‘be-cause nobody warned me it would take me so longto even start to feel better.’’ For many womenboth social and economic consequences wereprofound. ‘‘I get lots of nice social invitations.butI refuse a lot .I just have to miss out.’’ ‘‘I forgetmany things, I start doing one thing and then forgetwhat it was and end up doing something else.’’ ‘‘It’sa disempowering thing, because you’re not on deckwhen everything is happening in the family and atwork. At work you have to force yourself to stay awakeof course.’’ ‘‘At times I believe I’m living in a body 15

years older than it need be..’’ ‘‘But I haven’t reallygot right back into life. I don’t work.’’

Analysis of TranscriptsdCFS GroupsData from the CFS groups were analyzed us-

ing the same three level process. The initialcoding identified 80 symptoms. Interestingly,a number of very similar constructs emerged,with women using many almost identical de-scriptors to those used by the women withPCF (see Fig. 2). For example, in describingthe feeling of fatigue ‘‘.it is such an effort todo that simple task.,’’ ‘‘I feel like I have run a mar-athon.,’’ ‘‘the body is so tired, heavy,’’ ‘‘just com-plete lethargy and no energy.’’ Unrefreshingsleep was also a ubiquitous complaint: ‘‘I guessI don’t remember when I last woke up in the morningand actually felt refreshed,’’ ‘‘When you wake up youfeel like you haven’t slept.’’ Similarly, neurocogni-tive symptoms were described as ‘‘it’s really hardyou know.to remember words,’’ ‘‘I am often search-ing for the right word.’’ Although the categories


Fatigue

Abnormal tiredness:

“I am so tired & heavy that I can’t

stand.”

Lack of energy:

“complete lethargy & no energy...’’

Unrefreshing sleep:

“But I never wakeup fresh,not like I

used to...”

Fatigue

Abnormal tiredness:

“I’d get tired much earlier than usual”

Lack of energy:

“ and I have no energy...”

Unrefreshing sleep:

“I’d wake up & think…I’ve got nothing

out of this sleep at all...”

Somatic

‘Flu-like symptoms:

“...constantly feel like I am getting the

flu all the time.”

Musculo-skeletal:

“… muscle heaviness and aches and

pains...”

Abnormal sensitivities:

“I seem to be a lot more sensitive to

so much more foods.”

“like me with the smell ...”

Neurocognitive impairment

Impaired: –

Verbal fluency:

“ Its really hard - you know - to

remember words.”

Concentration:

“You read one sentence over & over

again.”

Memory:

“…brain won't work, I can't remember

anything.”

Neurocognitive impairment

Impaired: –

Verbal fluency:

“…I’m lost for words…”

Concentration:

“I start reading & my mind wanders…”

Memory :

“I have no memory…”

Mood Disturbance

Low Mood:

“I’ve started feeling sorry for

myself…”

Frustration:

“.... I get really upset…”

Anxiety:

“I am worried that something else

has gone wrong”

Mood Disturbance

Low Mood:

“…it does depress me…”

Frustration:

“. The most frustrating thing…. is I

want to be doing things and I can't”

Anxiety:

“ and then developing anxiety

about not coping...” (with work)

Post-cancer fatigue Chronic fatigue syndrome

Fig. 2. Comparison of the characteristics of PCF and CFSdanalysis of focus group transcripts.


comprising ‘‘fatigue,’’ ‘‘neurocognitive impair-ment,’’ and ‘‘mood disturbance’’ were essen-tially indistinguishable between the twogroups, women with CFS also commonly re-ported an additional category of somatic symp-toms. Many were of a musculoskeletal nature:‘‘I also get really bad muscle pains when I lay inbed,’’ ‘‘I wake up stiff and achy.like you’ve runaround the block all night,’’ ‘‘I have the most incred-ible pain in my joints.’’ A small number ofwomen with CFS also reported that they con-stantly felt as though they were ‘‘.getting theflu all the time.,’’ while others describedheightened sensitivity to light, noise, or odors(e.g., perfumes) ‘‘My sense of smell has become in-credibly heightened. I have discovered baby powder issomething that makes me feel really, really ill.’’

Closely analogous to the descriptions of thewomen with PCF, the women with CFS also re-ported physical, psychological, and behavioralconsequences of fatigue: ‘‘I have no energy andI can’t wait to get home from work. It’s sad becauseI never used to be like that’’; ‘‘I go to bed at 8 o’clock,half past 7 maybe.because I can’t stay up any lon-ger’’; ‘‘Last year I would have gone out about fourtimes, and I’m single, so that’s a great life isn’tit!’’; ‘‘I took time off because I realised that I was do-ing a very poor job in the classroom’’; ‘‘I think one ofthe most frustrating things was that I wanted to bedoing things and I just couldn’t.’’; ‘‘I found Iwas often searching for the word. I couldn’t actuallyfind the word I wanted . which being an Englishteacher was somewhat of a problem!’’

DiscussionProlonged fatigue states following cancer

treatment have been documented to causesubstantial reductions in quality of life andfunctional status.8,9,21 In common with otherfatigue syndromes, such as postinfectivefatigue22 and CFS,11,23 the underlying mecha-nisms of the illness are unknown. A fundamen-tal question is whether these illnesses shareclinical characteristics and potentially, there-fore, pathogenic mechanisms.

This report describes the spectrum of symp-toms in the unexplained fatigue state after oth-erwise successful treatment for early stagebreast cancer. Somatic, neurocognitive and af-fective symptoms were described, which led tosignificant negative physical, psychological,and social consequences. Earlier studies us-ing24,25 unstructured interviews were focused

on subjects still on treatment. The study re-ported here is the first to use the focus groupmethodology to provide an empirical descrip-tion of PCF in cancer survivors. In bothCRF26 and CFS,11 the diagnosis is currentlymade on the basis of criteria derived by expertconsensus rather than empirically derived da-tasets. It is generally reassuring to note thatthe 11 symptom criteria listed in the case defi-nition for CRF10 were disclosed by women inthis study. For instance, as expected, the com-plaint of fatigue was prominent in the sessions,and was consistent with the various descriptorsin the case definition (‘‘.disproportionate toany recent change in activity level’’; ‘‘post-exer-tional malaise lasting several hours’’). Mostwomen described the fatigue state as being ex-cessive in relation to the relatively limited phys-ical activity undertaken and protracted incourse. Similarly, impairments in concentra-tion and short-term memory were commonlyreported and are included in the case defini-tion. One commonly reported neurocognitivedisturbance, which is not a component of thedefinition, was difficulty with word finding.The case definition for PCF also lists a ‘‘per-ceived need to struggle to overcome inactivity’’as one of the 11 symptoms. This phenomenon,which is suggestive of motivational loss, was notdescribed by the participantsdinstead, thewomen generally reported that they struggledto overcome the limitations on physical andcognitive activity imposed by the fatigue state,which is more consistent with another elementof the definition, ‘‘difficulty completing dailytasks attributed to feeling fatigued.’’ This find-ing suggests that modification of the former el-ement of the diagnostic criteria should beconsidered.

An important feature of the descriptionsprovided by women with CRF was the elementof mood disturbance. This is noteworthy as fa-tigue may be the presenting complaint of pri-mary psychiatric disorders, including majordepression and anxiety.27,28 Up to 47% of pa-tients with cancer experience major depres-sion during or after adjuvant treatment,29

although in the presence of a physical disor-der, such psychiatric illness is often hard to for-mally diagnose (as symptoms such as fatigueoverlap between the diagnostic criteria).29,30

Although the women with CRF in this studywere excluded if an alternative medical or


psychiatric disorder could explain the fatiguestate, it is readily apparent that symptoms ofmood disturbance were prevalent. This findingargues against the arbitrary exclusion of pa-tients with major depression from the diagno-sis of CRFdinstead, a more sophisticatedconsideration of the symptom of depressedmood, and the possibility of comorbid majordepression as a syndromal diagnosis in con-junction with the fatigue state is warranted.

Another prominent element of the mooddisturbance in women with PCF was the fear(and associated anxiety) that the ongoing ill-ness may be a consequence of tumor recur-rence. In turn, this appeared to be related, atleast in part, to the discrepancy between the ill-ness experience and the expectations providedby the health care team, which suggested thatfollowing the end of adjuvant treatment, theywould rapidly feel better. This observationpoints to the need for a better recognition ofthe prevalence of CRF in the medical oncologysetting.

The symptom domains reported by womenwith CFS were remarkably similar to those de-scribed by women with CRF. Often womenused almost identical phrases to describe theindividual symptoms. The core symptom of fa-tigue, in particular, was described uniformly bythe two groups. Women with CFS did reportadditional somatic symptoms including thosedesignated as being influenza-like, as well asmusculoskeletal pain. This finding suggestsshared illness mechanisms in the two condi-tions. Several of the shared symptom domainshave been subjected to formal testing for ob-jective abnormality. For instance, studies ofneuromuscular performance in patients withCFS indicate that the phenomenon of fatigueis attributable to a central (i.e., in the brain),rather than a peripheral (i.e., in the nerve ormuscle) defect.31 No neuromuscular studiesin patients with CRF have been reported. Re-garding neurocognitive disturbance, a meta-analysis of 30 cross-sectional studies of formaltesting of cognition in CRF and two recent pro-spective cohort studies have found generallyconsistent impairments of executive function,verbal memory, and motor function.32e34

Similar impairments have been demonstratedin patients with CFS.35 However, in both con-texts the majority of subjects do not demon-strate objective impairments in cognitive

performance, highlighting the discrepancy inprevalence with the essentially universal symp-tom report.

A close relationship between fatigue andsleep disturbance was also evident in both sub-ject groups. In healthy individuals, adequaterest or sleep relieves physiological fatigue, re-sulting from physical exertion or sleep depriva-tion. However, women with PCF and CFSreported both hypersomnia (increased sleeprequirements) and an unrefreshing sleep qual-ity, but not other manifestations typical ofprimary sleep disorder such as daytime somno-lence. Formal polysomnography in patientswith CFS indicates that disturbances of sleepmaintenance (e.g., frequent awakenings, rest-less legs) are prevalent, but primary sleep dis-orders are rare.36 Formal sleep studies inpatients with PCF have not been reported.

A limitation of this study is that the womenstudied were purposefully selected as havingscored above a predetermined cut-off for fa-tigue states identified by questionnaire, andhaving met case definitions for PCF or CFS, in-cluding the requirement for exclusion of alter-native explanatory medical and psychiatricdisorders. Both stages of this prestudy evalua-tion may have influenced the type of patientsincluded and consequently the outcomes ofthe analysis of symptom reports. Nevertheless,the findings suggest both shared, and poten-tially divergent mechanisms of disease. Thepathogenesis of prolonged subjective fatiguestates remains obscure, with the exception ofacute infection, where such symptoms are be-lieved to be immunologically mediated viathe effects of proinflammatory cytokines onthe CNS.37 It has been hypothesized that simi-lar mechanisms may be implicated in the path-ogenesis of CRF38 and CFS.39

Further investigations of fatigue states inoncology and in other settings should takeaccount of these phenotypic similarities.

AcknowledgmentsThe generous support of all those women

who gave their time to participate in the studyis gratefully acknowledged.

References1. Early Breast Cancer Trialists’ Collaborative G.

Multi-agent chemotherapy for early breast cancer.Cochrane Database Syst Rev 2002; CD000487.


2. Tchen N, Juffs HG, Downie FP, et al. Cognitivefunction, fatigue, and menopausal symptoms inwomen receiving adjuvant chemotherapy for breastcancer. J Clin Oncol 2003;21:4175e4183.

3. Fossa SD, Dahl AA, Loge JH. Fatigue, anxiety,and depression in long-term survivors of testicularcancer. J Clin Oncol 2003;21:1249e1254.

4. Bower JE, Ganz PA, Desmond KA, et al. Fatiguein long-term breast carcinoma survivors: a longitudi-nal investigation. Cancer 2006;106:751e758.

5. Hjermstad MJ, Oldervoll L, Fossa SD, et al.Quality of life in long-term Hodgkin’s disease survi-vors with chronic fatigue. Eur J Cancer 2006;42:327e333.

6. Young KE, White CA. The prevalence and mod-erators of fatigue in people who have been success-fully treated for cancer. J Psychosom Res 2006;60:29e38.

7. Nieboer P, Buijs C, Rodenhuis S, et al. Fatigueand relating factors in high-risk breast cancer pa-tients treated with adjuvant standard or high-dosechemotherapy: a longitudinal study. J Clin Oncol2005;23:8296e8304.

8. Vogelzang NJ, Breibart W, Cella D, et al. Patient,caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey.Semin Haematol 1997;34:4e12.

9. Curt GA, Breitbart W, Cella D, et al. Impact ofcancer-related fatigue on the lives of patients: newfindings from the fatigue coalition. Oncologist2000;5:353e360.

10. Portenoy RK, Itri LM. Cancer-related fatigue:guidelines for evaluation and management. Oncolo-gist 1999;4:1e10.

11. Fukuda K, Straus SE, Hickie I, et al. The chronicfatigue syndrome: a comprehensive approach to itsdefinition and study. International Chronic FatigueSyndrome Study Group. Ann Intern Med 1994;121:953e959.

12. Hickie I, Davenport T, Wakefield D, et al. Viraland non-viral pathogens precipitate post-infectiveand chronic fatigue syndromes: a prospective co-hort study. BMJ 2006;333(7568):575e580.

13. Krueger RA. Focus groups: A practical guide forapplied research. California, London, New Delhi:Sage Publications, 1994.

14. Reiskin H, Gendrop S, Bowen A, et al. Collabo-ration between community nurses and nursing fac-ulty using substance abuse prevention focusgroups. Nursingconnections 1999;12:31e36.

15. Mays N, Pope C. Qualitative research: rigourand qualitative research. BMJ 1995;311:109e112.

16. Hickie IB, Davenport TA, Hadzi-Pavlovic D,et al. Development of a simple screening tool forcommon mental disorders in general practice.Med J Aust 2001;175:s10es17.

17. Koschera A, Hickie I, Hadzi-Pavlovic D, et al.Prolonged fatigue, anxiety and depression: explor-ing relationships in a primary care sample. Aust NZ J Psychiatry 1999;33:545e552.

18. Bennett B, Goldstein D, Lloyd A, et al. Fatigueand psychological distressdexploring the relation-ship in women treated for breast cancer. Eur J Can-cer 2004;40:1689e1695.

19. Strauss A, Corbin J. Basics of qualitative re-search: Grounded theory procedures and tech-niques. Newbury Park, London, New Delhi: SagePublications, 1990.

20. Richards TJ, Richards T. NUD.IST Users man-ual. Victoria: Qualitative Solutions and Research(QSR), La Trobe University, 1994.

21. Cella D. Factors influencing quality of life incancer patients: anaemia and fatigue. Semin Oncol1998;25:43e46.

22. White PD, Thomas JM, Amess J, et al. The exis-tence of a fatigue syndrome after glandular fever.Psychol Med 1995;25:907e916.

23. Prins JB, van der Meer JW, Bleijenberg G.Chronic fatigue syndrome. Lancet 2006;367:346e355.

24. Glaus A. Fatigue in patients with cancer. Analy-sis and assessment. Berlin Heidelberg: Springer-Verlag, 1998.

25. Magnusson K, Moller A, Ekman T, Wallgren A.A qualitative study to explore the experience of fa-tigue in cancer patients. Eur J Cancer Care 1999;8:224e232.

26. Cella D, Passik S, Jacobsen P, Breitbart W. Prog-ress toward guidelines for management of fatigue.Oncology 1998;12:369e377.

27. Hayes JR. Depression and chronic fatigue incancer patients. Prim Care 1991;18:327e339.

28. Hickie I, Lloyd AR, Wakefield D. Chronic fa-tigue syndrome: current perspectives on evaluationand management. Med J Aust 1995;163:314e318.

29. Ibbotson T, Maguire P, Selby P, et al. Screeningfor anxiety and depression in cancer patients: the ef-fects of disease and treatment. Eur J Cancer 1994;30A:37e40.

30. Wilkinson MJB, Barczak P. Psychiatric screeningin general practice: comparison of the GeneralHealth Questionnaire and the Hospital Anxiety De-pression scale. J R Coll Gen Pract 1988;38:311e313.

31. Schillings ML, Kalkman JS, van der Werf SP,et al. Diminished central activation during maximalvoluntary contraction in chronic fatigue syndrome.Clin Neurophysiol 2004;115:2518e2524.

32. Anderson-Hanley C, Sherman ML, Riggs R,et al. Neuropsychological effects of treatments foradults with cancer: a meta-analysis and review ofthe literature. J Int Neuropsychol Soc 2003;9:967e982.


33. Fan HG, Houede-Tchen N, Yi QL, et al. Fatigue,menopausal symptoms, and cognitive function inwomen after adjuvant chemotherapy for breast can-cer: 1- and 2-year follow-up of a prospective con-trolled study. J Clin Oncol 2005;23:8025e8032.

34. Wefel JS, Lenzi R, Theriault R, et al. ‘Chemo-brain’ in breast carcinoma. Cancer 2004;101:466e475.

35. Michiels V, Cluydts R. Neuropsychological func-tioning in chronic fatigue syndrome: a review. ActaPsychiatr Scand 2001;103:84e93.

36. Watson NF, Kapur V, Arguelles LM, et al. Com-parison of subjective and objective measures of

insomnia in monozygotic twins discordant forchronic fatigue syndrome. Sleep 2003;26:324e328.

37. Vollmer-Conna U, Fazou C, Cameron B, et al.Production of pro-inflammatory cytokines corre-lates with the symptoms of acute sickness behaviourin humans. Psychol Med 2004;34:1289e1297.

38. Bower JE, Ganz PA, Aziz N, et al. T-cell homeo-stasis in breast cancer survivors with persistentfatigue. J Natl Cancer Inst 2003;95:1165e1168.

39. Lloyd A, Wakefield D, Boughton C, Dwyer J. Im-munological abnormalities in the chronic fatiguesyndrome. Med J Aust 1989;151:122e124.

the experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative...

Documents