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Original Article
A Meta-analysis of Chemotherapy related Cognitive Impairment in Patients with Breast Cancer
Jin-Hee Park1, Sun Hyoung Bae2
Journal of Korean Academy of Nursing 2012;42(5):644-658.
DOI: https://doi.org/10.4040/jkan.2012.42.5.644
Published online: October 12, 2012

1College of Nursing, Ajou University, Suwon, Korea

2College of Nursing, Yonsei University, Seoul, Korea

1College of Nursing, Ajou University, Suwon, Korea

2College of Nursing, Yonsei University, Seoul, Korea

Address reprint requests to : Bae, Sun Hyoung San 5, Wonchon-dong, Yeongtong-gu, Suwon 443-721, Korea. Tel: +82-31-219-7019 Fax: +82-31-219-7020 E-mail: baega7695@hanmail.net
• Received: April 13, 2012   • Revised: April 25, 2012   • Accepted: September 21, 2012

Copyright © 2012 Korean Society of Nursing Science

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Purpose
    The purpose of this study was to evaluate the cognitive effects of chemotherapy in patients with breast cancer.
  • Methods
    Using several databases, prospective studies were collected up to August 2011. Of 2,106 publications identified, 12 met the inclusion criteria, and 8 studies were used to estimate the effect size of chemotherapy on cognitive impairment.
  • Results
    Twelve studies were done since 2005 and most of the research was performed in Europe or North America. Eight studies were used to generate effect size across the cognitive domains of attention/concentration, verbal and visual memory, executive function, visuospatial skill, language, and subjective cognitive function. Each of the cognitive domains showed small effect sizes (-0.02 ~ -0.26), indicating diminished cognitive function for the chemotherapy group compared with non-chemotherapy groups.
  • Conclusion
    Finding suggests that breast cancer patients who undergo chemotherapy may experience mild cognitive decline. Further study is needed to generate knowledge and guideline for interventions to address chemotherapy related cognitive impairment in these patients.
  • Keywords: Chemotherapy; Mild cognitive impairment; Attention; Memory; Breast neoplasms
Figure 1.
Flow diagram of study screening.
jkan-42-644f1.jpg
Table 1
Characteristics of Studies Included in the Systematic Review
Study ID C Country Sample Age (year), M±SD Education level Staging and treatment* Measurement Type of neuropsychological test† Other variables and tools‡ Quality assessment§ Included in meta-analysis
Ahles et al. (2010) U.S.A. BC, CTx (n=60) 51.7±7.1 No differences among groups Staging: Stage 0, I, II, III (Exact percentages were not reported) Standard-dose chemotherapy: 30% AC, 36.7% AC plus paciltaxel, 3.3% AC plus taxotere, 1.8% CAF, 11.7% CMF, 16.7% FEC Local treatment: 81% RTx HRTx: 80% tamoxifen or anastrozole T1: Baseline (before CTx) T2: 1 month T3: 6 months T4: 18 months after CTx CVLT; Color-word interference test (DKEFS); Digit symbol-coding; Distractibility, reaction time (CPT); Faces I & II; Grooved pegboard; Logical memory I & II; PASAT; Sorting test; Trail making test; Verbal fluency test; Vocabulary (WAIS) Anxiety (STAI) Depression (CES-D) Fatigue (FSI) Subjective cognitive ability (MASRQ) + Subjective cognitive function
BC, nonCTx (n=72) 56.6±8.3 Staging: Stage 0, I, II, III (Exact percentages were not reported) Local treatment: 72% RTx HRTx: 66% tamoxifen or anastrozole
Comparison (n=45) 52.9±10.0 Healthy women
Bender et al. (2006) Collins et al. U.S.A Canada BC, CTx (n=19) 40.1±6.5 No differences among groups No differences Staging: 32% Stage I, 68% Stage II Standard-dose chemotherapy: 40% AC, 40% AC plus a taxane, 20% CMF T1: Baseline T2: 1 week T3: 12 months after CTx Digit vigilance test; Four word short memory test; RAVLT; RCFT; Trail making test-B Anxiet (POMS) Depression (BDI-II) Fatigue (POMS) Subjective cognitive ability (PAOF) − Objective & subjective cognitive function Objective
BC, nonCTx (n=15) 44.1±3.5 Staging: 40% Stage I, 60% Stage II Standard-dose chemotherapy:
Standard-dose chemotherapy: 33% AC, 42% AC plus a taxane, 25% doxorubicin and a taxane HRTx: 100% tamoxifen
BC (n=12) 44.5±4.2 Staging: 100% DCIS
Collins et al. (2009) Canada BC, CTx (n=53) 57.9±3.7 No differences between groups Staging: 28.3% Stage I, 67.9% Stage II, 3.8% Stage III Standard-dose chemotherapy: 24.5% AC, 5.7% AC plus taxol, 9.4% CEF, 3.7% EC plus taxol, 5.7% FAC, 49.1% FEC, 1.9% Adriamycin and cisplatin HRTx: 11% tamoxifen, 4% arimidex, 2% letrozole T1: Baseline(before CTx) T2: 1 month T3: 12 months after CTx Arithmetic; Block design; Boston naming test; CVLT; Consonant trigrams; Phonemic word fluency(COWAT); Digit span-forward + backward; Digit symbol, Coding; Family pictures II; Grooved pegboard; Letter-number sequencing; PASAT; RVLT; Spatial span; Trail making test A or B; Wisconsin card sorting test Anxiety (POMS) Depression (POMS) Fatigue (POMS) + + Objective cognitive function
BC, nonCTx (n=40) 57.6±4.0 Staging: 87.5% Stage I, 12.5% Stage II
HRTx: 63% tamoxifen, 27% arimidex, 10% switched (tamoxifen to arimidex)
Debess et al. (2010) Denmark BC, CTx (n=75) BC, nonCTx (n=26) BC(n=19) 47.2 (Range: 29~59) 56.2 (Range: 44~59) 49.7 (Range: 39~59) No differences among groups Staging was not reported Standard-dose chemotherapy: 100% CEF Local treatment: 69% RTx Staging was not reported Local treatment: 65% RTx HRTx: tamoxifen 100% Staging was not reported Local treatment: 53% RTx T1: Baseline (before CTx) T2: 1 month after CTx Visual verbal learning test; Concept shifting test; Stroop color word interference test; Letter–digit coding test Anger (POMS) Confusion (POMS) Coping capacity (GPS) Depression (POMS) Fatigue (POMS) Quality of life (EORTC QLQ-C30) Subjective cognitive ability (SCF) Tension (POMS) + + No
Comparison (n=208) 48.1 (Range: 28~59) Healthy women
Fan et al. (2005) Canada BC, CTx (n=104) Median=48 No differences between groups Staging was not reported Standard-dose chemotherapy: 19% AC, 63% CEF, 18% other Local treatment: RTx, 6.7% at T1, 68.1% at T2, 65.4% at T3 HRTx: Tamoxifen or anastrozole, 4.8% at T1, 62.6% at T2, 66.7% at T3 T1: Baseline (before CTx) T2: 1 year T3: 2 years after CTx Conner’s continuous performance test; Trail making test Fatigue (FACT-F) Menopausal symptoms (FACT-ES) Quality of life (FACT-G) Subjective cognitive ability (HSCS) + No
Comparison (n=102) Median=47 Healthy women
Mehlsen et al. (2009) Denmark BC, CTx (n=36) Comparison (n=14) 48.6±8.0 39.3±11.7 Significant differences between groups (p=.001) Staging was not reported Standard-dose chemotherapy: 100% CEF Healthy people (6 males, 11 females) T1: Baseline (before CTx) T2: 4-6 weeks after CTx (Comparison: 3-4 months) Arithmetic; Coding & symbol search; Digit span, Forward or Backward; Letter-number sequencing; Logical memory; RAVLT; RCFT; Stroop test; Trail making test A & B; Word fluency test Confusion (POMS) Depression (BDI-II) Life satisfaction (SLS) Sleep quality (PSI) Social support (SSQT) Stress (PSS) + + Objective cognitive function
Noal et al. (2011) France France BC, CTx (n=161) Median=53 (Range: 31-71) No differences between groups Staging was not reported Standard-dose chemotherapy: 54% FEC, 30% FEC plus docetaxel, 16% other Local treatment: 100% RTx HRTx: 81% tamoxifen, anastrozole, or tamo+LH-RH analogue T1: Baseline T2: 3 weeks after baseline T3: End of RTx T4: 4 months T5: 12 months after RTx Digit span-forward or backward; RAVLT; Trail making test Quality of life(FACT-G) Fatigue(FACT-F) Anxiety(HADS) Depression(HADS) + + No
BC, nonCTx (n=141) Median=58 (Range: 36~84) Staging was not reported Local treatment: 100% RTx HRTx: 89% tamoxifen, anastrozole, or tamo+LH-RH analogue 89%
Ouimet et al. (2009) Canada BC, CTx (n=49) BC, nonCTx (n=46) Comparison (n=28) 57.5±3.9 57.5±4.2 59.4±4.1 Significant differences among groups (p=.014) Staging: Stage I, II (Exact percentages were not reported) Standard-dose chemotherapy: CEF, FAC, FEC (Exact percentages were not reported) Staging: Stage I, II (Exact percentages were not reported) HRTx: not reported Healthy women T1: Baseline (before CTx) T2: End of CTx (approximately within 6 months) Arithmetic; Block design; Boston naming test; CVLT; Consonant trigrams; COWAT; Digit span, forward + backward; Digit symbol-coding & symbol coding; Family pictures; Grooved pegboard; Letter–number sequencing; Logical memory; PASAT; RVLT; Spatial span; Trail making test A & B Psychological distress (POMS) − Objective cognitive function
Quesnel et al. (2009) Canada BC, CTx (n=41) 50.3±7.2 No differences among groups Staging: 34.1% Stage I, 48.8% Stage II, 17.1% Stage III Standard-dose chemotherapy: 56.1% AC, 14.6% FEC, 29.3% TAC Local treatment: 100% RTx HRTx: 75.6% T1: Baseline (before CTx or RTx) T2: Post CTx or RTx T3: 3 months after CTx or RTx Digit span; RAVLT; RCFT; Ruff 2 & 7 test; Symbol digit modalities test; Trail making test A & B; Verbal fluency test; Visual memory span (WMS-R) Quality of life (EORTC QLQ-C30) Subjective cognitive ability (CFQ) + + Objective & subjective cognitive function
BC, nonCTx (n=40) 57.7±4.9 Staging: 90.0% Stage I, 10.0% Stage II HRTx: 77.5%
Comparison (n=45); CCTx (n=23); CnonCTx (n=22) CCTx, 47.9±7.4; CnonCTx, 55.0±7.1 Healthy women
Shilling et al. (2005) U.K. BC, CTx (n=50) Comparison (n=43) 51.1±8.6 52.3±5.8 No differences between groups Staging was not reported Standard-dose chemotherapy: 2% AC, 2% CMF, 84% FEC, 12% FEC plus docetaxel HRTx: 28.0% Healthy women HRTx: 51.2% T1: Baseline (before CTx) T2: 1 month after CTx Digit span; Letter cancellation; Letter-number sequencing; Logical memory; RAVLT; RCFT; Spatial span; Stroop test Fatigue (FACT-F) General health (GHQ12) Menopausal symptoms (FACT-ES) Quality of life (FACT-B) Subjective cognitive ability (CFQ) ) + Objective & subjective cognitive function
Tager et al. (2010) U.S.A. BC, CTx (n=30) BC, nonCTx (n=31) 60.3±5.6 61.1±6.2 No differences between groups Staging: 30% Stage I, 70% Stage II Standard-dose chemotherapy: 23.3% AC, 46.7% ACT, 30.0% CMF Local treatment: 56.7% RTx HRTx: 40% Staging: 35.5% DCIS, 51.6% Stage I, 12.9% Stage II Local treatment: 64.5% RTx HRTx: 64.5% T1: Baseline (before CTx) T2: 1 month T3: 6 months after CTx Arithmetic; Benton visual retention test; Boston naming test; Busckle selective reminding test; COWAT; Digit span; Digit symbol; Finger tapping test; Grooved pegboard; Letter–number sequencing; RCFT; Trail making test Depression (BDI-II) Anxiety (ZAS) Subjective cognitive ability (interview) y + No
Vearncombe et al.(2009) Australia BC, CTx (n=136) BC, nonCTx (n=21) 49.4±7.9 54.0±8.2 No differences between groups Staging: 27.2% Stage I, 72.8% Stage II Standard-dose chemotherapy: 5.1% AC, 19.7% AC plus taxol/ taxotere, 8.9% CAF, 3.2% CEA, 0.6% CMF, 44.6% FEC, 3.2% FEC plus taxotere, 0.6% FEA, 0.6% Cyclophosphamide plus taxotere Staging: 81% Stage I, 19% Stage II Local treatment: not reported HRTx: not reported T1: Baseline (before CTx) T2: 1 month after CTx AVLT; COWAT; Digit Span-backward; Card sorting task (DKEFS); Matrix reasoning (WAIS-III); Purdue pegboard; Stroop test; Symbol digit modalities test; Test of everyday attention-visual elevator & telephone search; Visual reproduction (WMS-III) Anxiety and depression (HADS) Fatigue (FACT-F) Quality of life (FACT-B) + Objective cognitive function

* AC=Doxorubicin and cyclophosphamide; ACt=Doxorubicin, cyclophosphamide, and taxane; CAF=Cyclophosphamide, doxorubicin, and 5-fluorouracil; CEA=Cyclophosphamide, epirubicin, and adriamycin; CEF=Cyclophosphamide, epirubicin, and 5-fluorouracil; CMF=Cyclophosphamide, methotrexate, and 5-fluorouracil; EC=Epirubicin and cyclophosphamide; FAC=5-fluorouracil, doxorubicin, and cyclophosphamide; FEA=5-fluorouracil, epirubicin, and adriamycin; FEC=5-fluorouracil, epirubicin, and cyclophosphamide; LH-RH=Luteinizing hormone-releasing hormone; TAC=Taxotere, adriamycin, and cyclophosphamide.

†AVRT=Auditory verbal learning test; COWAT=Controlled oral word association test; CPT=Continuous performance test; CVLT=California verbal learning test; DKEFS=Delis-Kaplan executive function system; PASAT=Paced auditory serial addition test; RAVLT=Rey auditory verbal learning test; RCFT=Rey complex figure test; RVLT=Rey visual learning test; WAIS=Wechsler adult intelligence scale; WMS-III=Wechsler memory scale-version 3; WMS-R=Wechsler memory scale-revised.

‡BDI-II=Beck depression inventory-version 2; CES-D=Center for epidemiological study–depression; CFQ=Cognitive failures questionnaire; EORTC QLQ-C30=European organization for the research and treatment of cancer quality of life questionnaire; FACT-B=Functional assessment of cancer therapy scale - for breast cancer; FACT-ES=Functional assessment of cancer therapy scale – endocrine symptom; FACT-F=Functional assessment of cancer therapy scale – fatigue; FACT-G=Functional assessment of cancer therapy scale - general; FSI=Fatigue symptom inventory; GHQ12=General health questionnaire 12; GPS=General perceived self-efficacy; HADS=Hospital anxiety and depression scale; HSCS=High sensitivity cognitive screen; MASRQ=Multiple ability self-report questionnaire; PAOF=Patient’s assessment of own functioning; POMS=Profile of mood states; PSI=Pittsburgh sleep inventory; PSS=Perceived stress scale; SCF=Subjective cognitive functioning; SLS=Satisfaction with life scale; SSQt=Social support questionnaire of transactions; STAI=State trait anxiety inventory; ZAS=Zung anxiety scale.

§Quality assessment of literature by Scottish Intercollegiate Guidelines Network checklist. ‘+ +’ indicates that all or most of the criteria have been fulfilled. ‘+’ indicates that some of the criteria have been fulfilled. ‘-’ indicates fe or no criteria fulfilled.

Abbreviation: BC=Breast cancer; CCTx=Comparison group who matched with breast cancer treated with chemotherapy; CnonCTx=Comparison group who matched with breast cancer not treated with chemotherapy; CTx=Treated with chemotherapy; DCIS=Ductal carcinoma in situ; HRTx=Treated with hormone therapy; M=mean; nonCTx=Not treated with chemotherapy; RTx=Treated with radiotherapy; SD=Standard deviation; U.K.=United Kingdom; U.S.A.=United States of America.

Table 2.
Characteristics of 12 Research Studies (N=12)
Characteristics Categories n (%) Range
Publication year 2005 2 (16.7)
2006 1 (8.3)
2009 5 (41.7)
2010 3 (25.0)
2011 1 (8.3)
Region North America 7 (58.4)
Europe 4 (33.3)
Other 1 (8.3)
Sample size <50 1 (8.3) 46-328
50-100 4 (33.3)
≥101 7 (58.4)
Mean age of study participants (year) <50 3 (30.0)
50-60 6 (60.0)
≥61 1 (10.0)
Not reported 2
Instrument of subjective cognitive ability Cognitive failures questionnaire 2 (33.3)
Multiple ability self-report questionnaire 1 (16.7)
Patient's assessment of own functioning 1 (16.7)
Subjective cognitive functioning 1 (16.7)
Interview 1 (16.7)
Not measured 6
Post-test period after treatment (months) <1 3 (25.0) 0.25-12
1-3 4 7 2 (58.4) (16.7)
≥4 2 (16.7)
Follow up period after treatment (months) <6 6 12 5 4 (41.7) (33.3) 1-24
6-12 13 4 3 (33.3) (25.0)
≥13 3 (25.0)
Table 3.
Effect Sizes for Chemotherapy on Cognitive Function
Test No. of studies* n† Effect size‡ Lower 95% CI Upper 95% CI Z p Nfs
Attention/concentration 19 1,515 −0.14 −0.24 −0.03 2.57 .010 15
   Digit span-forward and backward 3 265 −0.08 −0.32 0.16 0.64 .524
   Digit span-forward 2 127 −0.24 −0.73 0.25 0.96 .337
   Trails making test-part A 5 392 −0.06 −0.27 0.14 0.61 .538
   Arithmetic 4 311 −0.06 −0.29 0.17 0.49 .626
   Letter-number sequencing 5 420 −0.28 −0.48 −0.08 2.78 .005
Memory 30 2,204 −0.17 −0.25 −0.08 3.66 <.001 73
   Verbal memory 20 1,602 −0.17 −0.28 −0.07 3.19 .001 32
   CVLT short delay free recall 3 265 −0.39 −0.64 −0.14 3.11 .002
   CVLT long delay free recall 3 265 −0.08 −0.33 0.16 0.68 .500
   CVLT long delay recognition 3 265 -0.06 -0.30 0.19 0.47 .636
   RAVLT immediate recall 6 458 −0.21 −0.41 0.00 1.94 .052
   RAVLT long delay recall 5 349 −0.11 −0.36 0.14 0.86 .392
   Visual memory 10 602 −0.15 −0.32 0.01 1.85 .063 0
   RCFT immediate recall 5 301 −0.19 −0.42 0.04 1.59 .113
   RCFT long delay recall 5 301 −0.12 −0.35 0.11 1.04 .297
Executive function 17 1,407 -0.08 -0.18 0.03 1.35 .176 0
   Digit symbol–coding subset 4 311 −0.09 −0.32 0.14 0.76 .444
   Digit symbol-symbol search subset 4 311 −0.09 −0.32 0.14 0.80 .421
   Trails making test-part B 5 392 −0.09 −0.30 0.11 0.90 .366
   Digit span-backward 4 393 −0.03 −0.24 0.19 0.24 .812
Visuospatial skill 2 127 −0.11 −0.47 0.26 0.58 .562 −
   RCFT copy 2 127 -0.11 -0.47 0.26 0.58 .562
Language 3 265 −0.02 −0.26 0.23 0.13 .902 0
   Boston naming test 3 265 −0.02 −0.26 0.23 0.13 .902
Subjective cognitive function 6 474 −0.26 −0.44 −0.07 2.76 .006 6

CI=Confidence interval; CVLT=California verbal learning test; Nfs=Fail-safe N; RAVLT=Rey auditory verbal learning test; RCFT=Rey complex figure test. *The number of studies included per cognitive domain;

†Total number of participants per effect size;

‡Weighted standardized mean difference.

  • Ahles T. A., Saykin A.J. 2002;Breast cancer chemotherapy-related cognitive dysfunction. Clinical Breast Cancer. 3(Suppl 3):S84–S90. http://dx.doi.org/10.3816/CBC.2002.s.018ArticlePubMed
  • Ahles T. A., Saykin A. J., McDonald B. C., Li Y., Furstenberg C. T., Hanscom B. S., et al. 2010;Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: Impact of age and cognitive reserve. Journal of Clinical Oncology. 28:4434–4440. http://dx.doi.org/10.1200/JCO.2009.27.0827ArticlePubMedPMC
  • Bender C. M., Sereika S. M., Berga S. L., Vogel V. G., Brufsky A. M., Paraska K. K., et al. 2006;Cognitive impairment associated with adjuvant therapy in breast cancer. Psycho-Oncology. 15:422–430. http://dx.doi.org/10.1002/pon.964ArticlePubMed
  • Braver T. S., Barch D.M. 2002;A theory of cognitive control, aging cognition, and neuromodulation. Neuroscience and Biobehavioral Reviews. 26:809–817. http://dx.doi.org/10.1016/S0149-7634(02)00067-2ArticlePubMed
  • Collins B., Mackenzie J., Stewart A., Bielajew C., Verma, S. 2009;Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psycho-Oncology. 18:134–143. http://dx.doi.org/10.1002/pon.1379ArticlePubMed
  • Cusimano, A. 2001.Learning disabilities: There is a cure. Pennsylvania, PA: Achieve Publications.
  • Debess J., Riis J. Ø., Engebjerg M. C., Ewertz, M. 2010;Cognitive function after adjuvant treatment for early breast cancer: A population-based longitudinal study. Breast Cancer Research and Treatment. 121:91–100. http://dx.doi.org/10.1007/s10549-010-0756-8ArticlePubMedPDF
  • DerSimonian R., Laird, N. 1986;Meta-analysis in clinical trials. Controlled Clinical Trials. 7:177–188. http://dx.doi.org/10.1016/0197-2456(86)90046-2ArticlePubMed
  • Egger M., Davey Smith G. D., Schneider M., Minder, C. 1997;Bias in meta-analysis detected by a simple, graphical test. British Medical Journal. 315:629–634. http://dx.doi.org/10.1136/bmj.315.7109.629ArticlePubMedPMC
  • Falleti M. G., Sanfilippo A., Maruff P., Weih L., Phillips K.A. 2005;The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: A meta-analysis of the current literature. Brain and Cognition. 59:60–70. http://dx.doi.org/10.1016/j.bandc.2005.05.001ArticlePubMed
  • Fan H. G., Houédé-Tchen N., Yi Q. L., Chemerynsky I., Downie F. P., Sa-bate K., et al. 2005;Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1-and 2-year follow-up of a prospective controlled study. Journal of Clinical Oncology. 23:8025–8032. http://dx.doi.org/10.1200/JCO.2005.01.6550ArticlePubMed
  • Gazzaniga M. S., Ivry R. B., Mangun G.R. 2002.Cognitive neuroscience: The biology of the mind. 2nd ed.New York, NY: W.W. Norton & Company.
  • Glogoski C., Milligan N. V., Wheatley C.J. 2006.Evaluation and treatment of cognitive dysfunction. In: Pendleton H.M., Schultz- Krohn W., editors. Pedretti’s occupational therapy: Practice skills for physical dysfunction. 6th ed. p. 589–608. St. Louis, MO: Mosby Elsevier.
  • Isaki E., Spaulding T. J., Plante, E. 2008;Contributions of language and memory demands to verbal memory performance in language-learning disabilities. Journal of Communication Disorders. 41:512–530. http://dx.doi.org/10.1016/j.jcomdis.2008.03.006ArticlePubMed
  • Jansen C. E., Miaskowski C. A., Dodd M. J., Dowling G.A. 2007;A meta-analysis of the sensitivity of various neuropsychological tests used to detect chemotherapy-induced cognitive impairment in patients with breast cancer. Oncology Nursing Forum. 34:997–1005. http://dx.doi.org/10.1188/07.ONF.997-1005ArticlePubMed
  • Kim G. D., Chung B. Y., Kim K. H., Byun H. S., Choi E.H. 2011;Analysis of a trend of instrument usage to assess cognitive function of breast cancer patients undergoing chemotherapy. Journal of Korean Oncology Nursing. 11:179–185. http://dx.doi.org/10.5388/jkon.2011.11.3.179ArticlePDF
  • Knobf M.T. 2011;Clinical update: Psychosocial responses in breast cancer survivors. Seminars in Oncology Nursing. 27:e1–e14. http://dx.doi.org/10.1016/j.soncn.2011.05.001Article
  • Korean National Statistical Office. 2009.Annual report on cause of death statistics. Seoul: Author.
  • Lezak M. D., Howieson D. B., Loring D.W. 2004.Neuropsychological assessment. 4th ed.New York, NY: Oxford University Press.
  • Matsuda T., Takayama T., Tashiro M., Nakamura Y., Ohashi Y., Shimo-zuma, K. 2005;Mild cognitive impairment after adjuvant chemotherapy in breast cancer patients-evaluation of appropriate research design and methodology to measure symptoms. Breast Cancer. 12:279–287. http://dx.doi.org/10.2325/jbcs.12.279ArticlePubMed
  • Myers J.S. 2009;Chemotherapy-related cognitive impairment. Clinical Journal of Oncology Nursing. 13:413–421. http://dx.doi.org/10.1188/09.CJON.413-421ArticlePubMed
  • National Evidence-based Healthcare Collaborating Agency. 2011.NE-CA’s guidance for systematic review for new health technology assessment. Seoul: Author.
  • Nelson C. J., Nandy N., Roth A.J. 2007;Chemotherapy and cognitive deficits: Mechanisms, findings, and potential interventions. Palliative and Supportive Care. 5:273–280. http://dx.doi.org/10.1017/S1478951507000442ArticlePubMed
  • Noal S., Levy C., Hardouin A., Rieux C., Heutte N., Ségura C., et al. 2011;One-year longitudinal study of fatigue, cognitive functions, and quality of life after adjuvant radiotherapy for breast cancer. International Journal of Radiation Oncology, Biology, Physics. 81:795–803. http://dx.doi.org/10.1016/j.ijrobp.2010.06.037ArticlePubMed
  • Ouimet L. A., Stewart A., Collins B., Schindler D., Bielajew, C. 2009;Measuring neuropsychological change following breast cancer treatment: An analysis of statistical models. Journal of Clinical and Experimental Neuropsychology. 31:73–89. http://dx.doi.org/10.1080/13803390801992725ArticlePubMed
  • Quesnel C., Savard J., Ivers, H. 2009;Cognitive impairments associated with breast cancer treatments: Results from a longitudinal study. Breast Cancer Research and Treatment. 116:113–123. http://dx.doi.org/10.1007/s10549-008-0114-2ArticlePubMedPDF
  • Rosenthal, R. 1991.Meta-analytic procedures for social research. Newbury Park, CA: Sage Publications.
  • Scottish Intercollegiate Guidelines Network. 2011;SIGN 50: A guideline developer's handbook. Retrieved January, 11, 2012, from. http://www.sign.ac.uk/pdf/sign50.pdf
  • Stewart A., Bielajew C., Collins B., Parkinson M., Tomiak, E. 2006;A meta-analysis of the neuropsychological effects of adjuvant chemotherapy treatment in women treated for breast cancer. The Clinical Neuropsychologist. 20:76–89. http://dx.doi.org/10.1080/138540491005875ArticlePubMed
  • Tager F. A., McKinley P. S., Schnabel F. R., El-Tamer M., Cheung Y. K., Fang Y., et al. 2010;The cognitive effects of chemotherapy in post- menopausal breast cancer patients: A controlled longitudinal study. Breast cancer Research and Treatment. 123:25–34. http://dx.doi.org/10.1007/s10549-009-0606-8ArticlePDF

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        A Meta-analysis of Chemotherapy related Cognitive Impairment in Patients with Breast Cancer
        J Korean Acad Nurs. 2012;42(5):644-658.   Published online October 12, 2012
        DOI: https://doi.org/10.4040/jkan.2012.42.5.644
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      A Meta-analysis of Chemotherapy related Cognitive Impairment in Patients with Breast Cancer
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      Figure 1. Flow diagram of study screening.

      Figure 1.

      A Meta-analysis of Chemotherapy related Cognitive Impairment in Patients with Breast Cancer
      Study ID C Country Sample Age (year), M±SD Education level Staging and treatment* Measurement Type of neuropsychological test† Other variables and tools‡ Quality assessment§ Included in meta-analysis
      Ahles et al. (2010) U.S.A. BC, CTx (n=60) 51.7±7.1 No differences among groups Staging: Stage 0, I, II, III (Exact percentages were not reported) Standard-dose chemotherapy: 30% AC, 36.7% AC plus paciltaxel, 3.3% AC plus taxotere, 1.8% CAF, 11.7% CMF, 16.7% FEC Local treatment: 81% RTx HRTx: 80% tamoxifen or anastrozole T1: Baseline (before CTx) T2: 1 month T3: 6 months T4: 18 months after CTx CVLT; Color-word interference test (DKEFS); Digit symbol-coding; Distractibility, reaction time (CPT); Faces I & II; Grooved pegboard; Logical memory I & II; PASAT; Sorting test; Trail making test; Verbal fluency test; Vocabulary (WAIS) Anxiety (STAI) Depression (CES-D) Fatigue (FSI) Subjective cognitive ability (MASRQ) + Subjective cognitive function
      BC, nonCTx (n=72) 56.6±8.3 Staging: Stage 0, I, II, III (Exact percentages were not reported) Local treatment: 72% RTx HRTx: 66% tamoxifen or anastrozole
      Comparison (n=45) 52.9±10.0 Healthy women
      Bender et al. (2006) Collins et al. U.S.A Canada BC, CTx (n=19) 40.1±6.5 No differences among groups No differences Staging: 32% Stage I, 68% Stage II Standard-dose chemotherapy: 40% AC, 40% AC plus a taxane, 20% CMF T1: Baseline T2: 1 week T3: 12 months after CTx Digit vigilance test; Four word short memory test; RAVLT; RCFT; Trail making test-B Anxiet (POMS) Depression (BDI-II) Fatigue (POMS) Subjective cognitive ability (PAOF) − Objective & subjective cognitive function Objective
      BC, nonCTx (n=15) 44.1±3.5 Staging: 40% Stage I, 60% Stage II Standard-dose chemotherapy:
      Standard-dose chemotherapy: 33% AC, 42% AC plus a taxane, 25% doxorubicin and a taxane HRTx: 100% tamoxifen
      BC (n=12) 44.5±4.2 Staging: 100% DCIS
      Collins et al. (2009) Canada BC, CTx (n=53) 57.9±3.7 No differences between groups Staging: 28.3% Stage I, 67.9% Stage II, 3.8% Stage III Standard-dose chemotherapy: 24.5% AC, 5.7% AC plus taxol, 9.4% CEF, 3.7% EC plus taxol, 5.7% FAC, 49.1% FEC, 1.9% Adriamycin and cisplatin HRTx: 11% tamoxifen, 4% arimidex, 2% letrozole T1: Baseline(before CTx) T2: 1 month T3: 12 months after CTx Arithmetic; Block design; Boston naming test; CVLT; Consonant trigrams; Phonemic word fluency(COWAT); Digit span-forward + backward; Digit symbol, Coding; Family pictures II; Grooved pegboard; Letter-number sequencing; PASAT; RVLT; Spatial span; Trail making test A or B; Wisconsin card sorting test Anxiety (POMS) Depression (POMS) Fatigue (POMS) + + Objective cognitive function
      BC, nonCTx (n=40) 57.6±4.0 Staging: 87.5% Stage I, 12.5% Stage II
      HRTx: 63% tamoxifen, 27% arimidex, 10% switched (tamoxifen to arimidex)
      Debess et al. (2010) Denmark BC, CTx (n=75) BC, nonCTx (n=26) BC(n=19) 47.2 (Range: 29~59) 56.2 (Range: 44~59) 49.7 (Range: 39~59) No differences among groups Staging was not reported Standard-dose chemotherapy: 100% CEF Local treatment: 69% RTx Staging was not reported Local treatment: 65% RTx HRTx: tamoxifen 100% Staging was not reported Local treatment: 53% RTx T1: Baseline (before CTx) T2: 1 month after CTx Visual verbal learning test; Concept shifting test; Stroop color word interference test; Letter–digit coding test Anger (POMS) Confusion (POMS) Coping capacity (GPS) Depression (POMS) Fatigue (POMS) Quality of life (EORTC QLQ-C30) Subjective cognitive ability (SCF) Tension (POMS) + + No
      Comparison (n=208) 48.1 (Range: 28~59) Healthy women
      Fan et al. (2005) Canada BC, CTx (n=104) Median=48 No differences between groups Staging was not reported Standard-dose chemotherapy: 19% AC, 63% CEF, 18% other Local treatment: RTx, 6.7% at T1, 68.1% at T2, 65.4% at T3 HRTx: Tamoxifen or anastrozole, 4.8% at T1, 62.6% at T2, 66.7% at T3 T1: Baseline (before CTx) T2: 1 year T3: 2 years after CTx Conner’s continuous performance test; Trail making test Fatigue (FACT-F) Menopausal symptoms (FACT-ES) Quality of life (FACT-G) Subjective cognitive ability (HSCS) + No
      Comparison (n=102) Median=47 Healthy women
      Mehlsen et al. (2009) Denmark BC, CTx (n=36) Comparison (n=14) 48.6±8.0 39.3±11.7 Significant differences between groups (p=.001) Staging was not reported Standard-dose chemotherapy: 100% CEF Healthy people (6 males, 11 females) T1: Baseline (before CTx) T2: 4-6 weeks after CTx (Comparison: 3-4 months) Arithmetic; Coding & symbol search; Digit span, Forward or Backward; Letter-number sequencing; Logical memory; RAVLT; RCFT; Stroop test; Trail making test A & B; Word fluency test Confusion (POMS) Depression (BDI-II) Life satisfaction (SLS) Sleep quality (PSI) Social support (SSQT) Stress (PSS) + + Objective cognitive function
      Noal et al. (2011) France France BC, CTx (n=161) Median=53 (Range: 31-71) No differences between groups Staging was not reported Standard-dose chemotherapy: 54% FEC, 30% FEC plus docetaxel, 16% other Local treatment: 100% RTx HRTx: 81% tamoxifen, anastrozole, or tamo+LH-RH analogue T1: Baseline T2: 3 weeks after baseline T3: End of RTx T4: 4 months T5: 12 months after RTx Digit span-forward or backward; RAVLT; Trail making test Quality of life(FACT-G) Fatigue(FACT-F) Anxiety(HADS) Depression(HADS) + + No
      BC, nonCTx (n=141) Median=58 (Range: 36~84) Staging was not reported Local treatment: 100% RTx HRTx: 89% tamoxifen, anastrozole, or tamo+LH-RH analogue 89%
      Ouimet et al. (2009) Canada BC, CTx (n=49) BC, nonCTx (n=46) Comparison (n=28) 57.5±3.9 57.5±4.2 59.4±4.1 Significant differences among groups (p=.014) Staging: Stage I, II (Exact percentages were not reported) Standard-dose chemotherapy: CEF, FAC, FEC (Exact percentages were not reported) Staging: Stage I, II (Exact percentages were not reported) HRTx: not reported Healthy women T1: Baseline (before CTx) T2: End of CTx (approximately within 6 months) Arithmetic; Block design; Boston naming test; CVLT; Consonant trigrams; COWAT; Digit span, forward + backward; Digit symbol-coding & symbol coding; Family pictures; Grooved pegboard; Letter–number sequencing; Logical memory; PASAT; RVLT; Spatial span; Trail making test A & B Psychological distress (POMS) − Objective cognitive function
      Quesnel et al. (2009) Canada BC, CTx (n=41) 50.3±7.2 No differences among groups Staging: 34.1% Stage I, 48.8% Stage II, 17.1% Stage III Standard-dose chemotherapy: 56.1% AC, 14.6% FEC, 29.3% TAC Local treatment: 100% RTx HRTx: 75.6% T1: Baseline (before CTx or RTx) T2: Post CTx or RTx T3: 3 months after CTx or RTx Digit span; RAVLT; RCFT; Ruff 2 & 7 test; Symbol digit modalities test; Trail making test A & B; Verbal fluency test; Visual memory span (WMS-R) Quality of life (EORTC QLQ-C30) Subjective cognitive ability (CFQ) + + Objective & subjective cognitive function
      BC, nonCTx (n=40) 57.7±4.9 Staging: 90.0% Stage I, 10.0% Stage II HRTx: 77.5%
      Comparison (n=45); CCTx (n=23); CnonCTx (n=22) CCTx, 47.9±7.4; CnonCTx, 55.0±7.1 Healthy women
      Shilling et al. (2005) U.K. BC, CTx (n=50) Comparison (n=43) 51.1±8.6 52.3±5.8 No differences between groups Staging was not reported Standard-dose chemotherapy: 2% AC, 2% CMF, 84% FEC, 12% FEC plus docetaxel HRTx: 28.0% Healthy women HRTx: 51.2% T1: Baseline (before CTx) T2: 1 month after CTx Digit span; Letter cancellation; Letter-number sequencing; Logical memory; RAVLT; RCFT; Spatial span; Stroop test Fatigue (FACT-F) General health (GHQ12) Menopausal symptoms (FACT-ES) Quality of life (FACT-B) Subjective cognitive ability (CFQ) ) + Objective & subjective cognitive function
      Tager et al. (2010) U.S.A. BC, CTx (n=30) BC, nonCTx (n=31) 60.3±5.6 61.1±6.2 No differences between groups Staging: 30% Stage I, 70% Stage II Standard-dose chemotherapy: 23.3% AC, 46.7% ACT, 30.0% CMF Local treatment: 56.7% RTx HRTx: 40% Staging: 35.5% DCIS, 51.6% Stage I, 12.9% Stage II Local treatment: 64.5% RTx HRTx: 64.5% T1: Baseline (before CTx) T2: 1 month T3: 6 months after CTx Arithmetic; Benton visual retention test; Boston naming test; Busckle selective reminding test; COWAT; Digit span; Digit symbol; Finger tapping test; Grooved pegboard; Letter–number sequencing; RCFT; Trail making test Depression (BDI-II) Anxiety (ZAS) Subjective cognitive ability (interview) y + No
      Vearncombe et al.(2009) Australia BC, CTx (n=136) BC, nonCTx (n=21) 49.4±7.9 54.0±8.2 No differences between groups Staging: 27.2% Stage I, 72.8% Stage II Standard-dose chemotherapy: 5.1% AC, 19.7% AC plus taxol/ taxotere, 8.9% CAF, 3.2% CEA, 0.6% CMF, 44.6% FEC, 3.2% FEC plus taxotere, 0.6% FEA, 0.6% Cyclophosphamide plus taxotere Staging: 81% Stage I, 19% Stage II Local treatment: not reported HRTx: not reported T1: Baseline (before CTx) T2: 1 month after CTx AVLT; COWAT; Digit Span-backward; Card sorting task (DKEFS); Matrix reasoning (WAIS-III); Purdue pegboard; Stroop test; Symbol digit modalities test; Test of everyday attention-visual elevator & telephone search; Visual reproduction (WMS-III) Anxiety and depression (HADS) Fatigue (FACT-F) Quality of life (FACT-B) + Objective cognitive function
      Characteristics Categories n (%) Range
      Publication year 2005 2 (16.7)
      2006 1 (8.3)
      2009 5 (41.7)
      2010 3 (25.0)
      2011 1 (8.3)
      Region North America 7 (58.4)
      Europe 4 (33.3)
      Other 1 (8.3)
      Sample size <50 1 (8.3) 46-328
      50-100 4 (33.3)
      ≥101 7 (58.4)
      Mean age of study participants (year) <50 3 (30.0)
      50-60 6 (60.0)
      ≥61 1 (10.0)
      Not reported 2
      Instrument of subjective cognitive ability Cognitive failures questionnaire 2 (33.3)
      Multiple ability self-report questionnaire 1 (16.7)
      Patient's assessment of own functioning 1 (16.7)
      Subjective cognitive functioning 1 (16.7)
      Interview 1 (16.7)
      Not measured 6
      Post-test period after treatment (months) <1 3 (25.0) 0.25-12
      1-3 4 7 2 (58.4) (16.7)
      ≥4 2 (16.7)
      Follow up period after treatment (months) <6 6 12 5 4 (41.7) (33.3) 1-24
      6-12 13 4 3 (33.3) (25.0)
      ≥13 3 (25.0)
      Test No. of studies* n† Effect size‡ Lower 95% CI Upper 95% CI Z p Nfs
      Attention/concentration 19 1,515 −0.14 −0.24 −0.03 2.57 .010 15
         Digit span-forward and backward 3 265 −0.08 −0.32 0.16 0.64 .524
         Digit span-forward 2 127 −0.24 −0.73 0.25 0.96 .337
         Trails making test-part A 5 392 −0.06 −0.27 0.14 0.61 .538
         Arithmetic 4 311 −0.06 −0.29 0.17 0.49 .626
         Letter-number sequencing 5 420 −0.28 −0.48 −0.08 2.78 .005
      Memory 30 2,204 −0.17 −0.25 −0.08 3.66 <.001 73
         Verbal memory 20 1,602 −0.17 −0.28 −0.07 3.19 .001 32
         CVLT short delay free recall 3 265 −0.39 −0.64 −0.14 3.11 .002
         CVLT long delay free recall 3 265 −0.08 −0.33 0.16 0.68 .500
         CVLT long delay recognition 3 265 -0.06 -0.30 0.19 0.47 .636
         RAVLT immediate recall 6 458 −0.21 −0.41 0.00 1.94 .052
         RAVLT long delay recall 5 349 −0.11 −0.36 0.14 0.86 .392
         Visual memory 10 602 −0.15 −0.32 0.01 1.85 .063 0
         RCFT immediate recall 5 301 −0.19 −0.42 0.04 1.59 .113
         RCFT long delay recall 5 301 −0.12 −0.35 0.11 1.04 .297
      Executive function 17 1,407 -0.08 -0.18 0.03 1.35 .176 0
         Digit symbol–coding subset 4 311 −0.09 −0.32 0.14 0.76 .444
         Digit symbol-symbol search subset 4 311 −0.09 −0.32 0.14 0.80 .421
         Trails making test-part B 5 392 −0.09 −0.30 0.11 0.90 .366
         Digit span-backward 4 393 −0.03 −0.24 0.19 0.24 .812
      Visuospatial skill 2 127 −0.11 −0.47 0.26 0.58 .562 −
         RCFT copy 2 127 -0.11 -0.47 0.26 0.58 .562
      Language 3 265 −0.02 −0.26 0.23 0.13 .902 0
         Boston naming test 3 265 −0.02 −0.26 0.23 0.13 .902
      Subjective cognitive function 6 474 −0.26 −0.44 −0.07 2.76 .006 6
      Table 1 Characteristics of Studies Included in the Systematic Review

      * AC=Doxorubicin and cyclophosphamide; ACt=Doxorubicin, cyclophosphamide, and taxane; CAF=Cyclophosphamide, doxorubicin, and 5-fluorouracil; CEA=Cyclophosphamide, epirubicin, and adriamycin; CEF=Cyclophosphamide, epirubicin, and 5-fluorouracil; CMF=Cyclophosphamide, methotrexate, and 5-fluorouracil; EC=Epirubicin and cyclophosphamide; FAC=5-fluorouracil, doxorubicin, and cyclophosphamide; FEA=5-fluorouracil, epirubicin, and adriamycin; FEC=5-fluorouracil, epirubicin, and cyclophosphamide; LH-RH=Luteinizing hormone-releasing hormone; TAC=Taxotere, adriamycin, and cyclophosphamide.

      †AVRT=Auditory verbal learning test; COWAT=Controlled oral word association test; CPT=Continuous performance test; CVLT=California verbal learning test; DKEFS=Delis-Kaplan executive function system; PASAT=Paced auditory serial addition test; RAVLT=Rey auditory verbal learning test; RCFT=Rey complex figure test; RVLT=Rey visual learning test; WAIS=Wechsler adult intelligence scale; WMS-III=Wechsler memory scale-version 3; WMS-R=Wechsler memory scale-revised.

      ‡BDI-II=Beck depression inventory-version 2; CES-D=Center for epidemiological study–depression; CFQ=Cognitive failures questionnaire; EORTC QLQ-C30=European organization for the research and treatment of cancer quality of life questionnaire; FACT-B=Functional assessment of cancer therapy scale - for breast cancer; FACT-ES=Functional assessment of cancer therapy scale – endocrine symptom; FACT-F=Functional assessment of cancer therapy scale – fatigue; FACT-G=Functional assessment of cancer therapy scale - general; FSI=Fatigue symptom inventory; GHQ12=General health questionnaire 12; GPS=General perceived self-efficacy; HADS=Hospital anxiety and depression scale; HSCS=High sensitivity cognitive screen; MASRQ=Multiple ability self-report questionnaire; PAOF=Patient’s assessment of own functioning; POMS=Profile of mood states; PSI=Pittsburgh sleep inventory; PSS=Perceived stress scale; SCF=Subjective cognitive functioning; SLS=Satisfaction with life scale; SSQt=Social support questionnaire of transactions; STAI=State trait anxiety inventory; ZAS=Zung anxiety scale.

      §Quality assessment of literature by Scottish Intercollegiate Guidelines Network checklist. ‘+ +’ indicates that all or most of the criteria have been fulfilled. ‘+’ indicates that some of the criteria have been fulfilled. ‘-’ indicates fe or no criteria fulfilled.

      Abbreviation: BC=Breast cancer; CCTx=Comparison group who matched with breast cancer treated with chemotherapy; CnonCTx=Comparison group who matched with breast cancer not treated with chemotherapy; CTx=Treated with chemotherapy; DCIS=Ductal carcinoma in situ; HRTx=Treated with hormone therapy; M=mean; nonCTx=Not treated with chemotherapy; RTx=Treated with radiotherapy; SD=Standard deviation; U.K.=United Kingdom; U.S.A.=United States of America.

      Table 2. Characteristics of 12 Research Studies (N=12)

      Table 3. Effect Sizes for Chemotherapy on Cognitive Function

      CI=Confidence interval; CVLT=California verbal learning test; Nfs=Fail-safe N; RAVLT=Rey auditory verbal learning test; RCFT=Rey complex figure test. *The number of studies included per cognitive domain;

      Total number of participants per effect size;

      Weighted standardized mean difference.

      Table 1

      Table 2.

      Table 3.

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