. 2012 Aug; 30(29):3578-87.
doi: 10.1200/JCO.2011.39.5640.

Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy

Heather S L Jim 1 Kristin M Phillips  Sari Chait  Leigh Anne Faul  Mihaela A Popa  Yun-Hsiang Lee  Mallory G Hussin  Paul B Jacobsen  Brent J Small  
  • PMID: 22927526
  •     56 References
  •     129 citations


Purpose: Evidence is mixed regarding long-term cognitive deficits in patients treated with chemotherapy. Previous meta-analyses have not focused specifically on the postchemotherapy period and have not incorporated several recent studies. The goal of the current study was to conduct a meta-analysis of cognitive functioning in breast cancer survivors who were treated with chemotherapy ≥ 6 months previously.

Methods: A search of PubMed, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library yielded 2,751 abstracts, which were independently evaluated by pairs of raters. Meta-analysis was conducted on 17 studies of 807 patients previously treated with standard-dose chemotherapy for breast cancer. Neuropsychological tests were categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.

Results: Deficits in cognitive functioning were observed in patients treated with chemotherapy relative to controls or prechemotherapy baseline in the domains of verbal ability (g = -0.19; P < .01) and visuospatial ability (g = -0.27; P < .01). Patients treated with chemotherapy performed worse than noncancer controls in verbal ability and worse than patients treated without chemotherapy in visuospatial ability (both P < .01). Age, education, time since treatment, and endocrine therapy did not moderate observed cognitive deficits in verbal ability or visuospatial ability (all P ≥ .51).

Conclusion: Results indicate that, on average, observed cognitive deficits in patients with breast cancer previously treated with chemotherapy are small in magnitude and limited to the domains of verbal ability and visuospatial ability. This information can be used to inform interventions to educate patients with breast cancer regarding the long-term impact of chemotherapy on cognitive functioning.

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Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance).
Jeanne S Mandelblatt, Jonathan D Clapp, +15 authors, Claudine Isaacs.
Cancer, 2016 Jul 23; 122(22). PMID: 27447359    Free PMC article.
Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.
Marie Lange, Natacha Heutte, +14 authors, Florence Joly.
Oncologist, 2016 Jul 31; 21(11). PMID: 27473044    Free PMC article.
The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.
Teresa Lesiuk.
Healthcare (Basel), 2016 Aug 16; 4(3). PMID: 27517966    Free PMC article.
Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer.
Lauren E Himmel, Maryam B Lustberg, +3 authors, Samuel K Kulp.
Exp Toxicol Pathol, 2016 Aug 25; 68(9). PMID: 27555377    Free PMC article.
Quality of life (QOL) and symptom burden (SB) in patients with breast cancer.
Julia Hamer, Rachel McDonald, +12 authors, Edward Chow.
Support Care Cancer, 2016 Oct 04; 25(2). PMID: 27696078
Memory and Spatial Cognition in Breast Cancer Patients Undergoing Adjuvant Endocrine Therapy.
Ute Berndt, Bernd Leplow, +3 authors, Christoph Thomssen.
Breast Care (Basel), 2016 Oct 11; 11(4). PMID: 27721710    Free PMC article.
Cognitive behavioral therapy for cancer-related cognitive dysfunction.
Shelly Kucherer, Robert J Ferguson.
Curr Opin Support Palliat Care, 2016 Nov 30; 11(1). PMID: 27898511    Free PMC article.
The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.
Huaidong Cheng, Wen Li, +3 authors, Kai Wang.
Am J Transl Res, 2016 Dec 03; 8(11). PMID: 27904710    Free PMC article.
Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy.
San-Gang Wu, Jia-Yuan Sun, +2 authors, Zhen-Yu He.
Ther Clin Risk Manag, 2016 Dec 23; 12. PMID: 28008263    Free PMC article.
Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors.
Huaidong Cheng, Wen Li, +5 authors, Kai Wang.
Sci Rep, 2017 Mar 23; 7. PMID: 28327626    Free PMC article.
Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression.
Wen Li, Chen Gan, +2 authors, Huaidong Cheng.
Medicine (Baltimore), 2017 Mar 30; 96(13). PMID: 28353608    Free PMC article.
Systemic therapies and cognitive impairment for breast cancer: an overview of the current literature.
Icro Meattini, Isacco Desideri, +5 authors, Lorenzo Livi.
Med Oncol, 2017 Apr 02; 34(5). PMID: 28364269
Management of Potential Long-Term Toxicities in Breast Cancer Patients.
C C O'Sullivan, K J Ruddy.
Curr Breast Cancer Rep, 2017 May 16; 8(4). PMID: 28503254    Free PMC article.
Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics.
Tamara E Lacourt, Cobi J Heijnen.
Curr Breast Cancer Rep, 2017 Jun 16; 9(2). PMID: 28616125    Free PMC article.
Abnormal Development of Dendrites in Adult-Born Rat Hippocampal Granule Cells Induced by Cyclophosphamide.
Lin Wu, Dandan Guo, +5 authors, Ren-Zhi Zhan.
Front Cell Neurosci, 2017 Jul 07; 11. PMID: 28680394    Free PMC article.
A novel preventive therapy for paclitaxel-induced cognitive deficits: preclinical evidence from C57BL/6 mice.
P Huehnchen, W Boehmerle, +2 authors, M Endres.
Transl Psychiatry, 2017 Aug 02; 7(8). PMID: 28763058    Free PMC article.
Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study.
Konstantinos Bromis, Kostakis Gkiatis, +6 authors, Vasileios Kouloulias.
Comput Math Methods Med, 2017 Aug 12; 2017. PMID: 28798808    Free PMC article.
Cognitive functioning and quality of life following chemotherapy in pre- and peri-menopausal women with breast cancer.
Jennifer R Klemp, Jamie S Myers, +4 authors, Annette L Stanton.
Support Care Cancer, 2017 Aug 30; 26(2). PMID: 28849337    Free PMC article.
Chemotherapy-induced changes of cerebral activity in resting-state functional magnetic resonance imaging and cerebral white matter in diffusion tensor imaging.
Caiqin Mo, Hailong Lin, +8 authors, Xiangjin Chen.
Oncotarget, 2017 Nov 09; 8(46). PMID: 29113386    Free PMC article.
Modifiable correlates of perceived cognitive function in breast cancer survivors up to 10 years after chemotherapy completion.
Ashley Henneghan, Alexa Stuifbergen, +2 authors, Elisabeth King.
J Cancer Surviv, 2017 Nov 09; 12(2). PMID: 29116555
Emotional distress and dysfunctional illness perception are associated with low mental and physical quality of life in Chinese breast cancer patients.
Lili Tang, Kurt Fritzsche, +8 authors, Rainer Schaefert.
Health Qual Life Outcomes, 2017 Dec 02; 15(1). PMID: 29191208    Free PMC article.
Changes in cognition and dendritic complexity following intrathecal methotrexate and cytarabine treatment in a juvenile murine model.
Tyler C Alexander, Christy M Simecka, +6 authors, Antiño R Allen.
Behav Brain Res, 2017 Dec 13; 346. PMID: 29229546    Free PMC article.
Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors.
Sarah J O Nomura, Yi-Ting Hwang, +8 authors, Judy Huei-Yu Wang.
Breast Cancer Res Treat, 2017 Dec 13; 168(2). PMID: 29230660    Free PMC article.
Survivorship care plans for breast cancer patients: understanding the quality of the available evidence.
V D'Souza, H Daudt, A Kazanjian.
Curr Oncol, 2017 Dec 23; 24(6). PMID: 29270054    Free PMC article.
Altered network efficiency of functional brain networks in patients with breast cancer after chemotherapy.
Han Xuan, Chen Gan, +5 authors, Huaidong Cheng.
Oncotarget, 2017 Dec 30; 8(62). PMID: 29285280    Free PMC article.
Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures.
M Simó, A Gurtubay-Antolin, +2 authors, A Rodríguez-Fornells.
Neuroimage Clin, 2018 Feb 02; 18. PMID: 29387526    Free PMC article.
Cognitive Impairment Associated with Cancer: A Brief Review.
J Cara Pendergrass, Steven D Targum, John E Harrison.
Innov Clin Neurosci, 2018 Mar 03; 15(1-2). PMID: 29497579    Free PMC article.
FORECAST - A cloud-based personalized intelligent virtual coaching platform for the well-being of cancer patients.
Sofoklis Kyriazakos, Vincenzo Valentini, Alfredo Cesario, Robert Zachariae.
Clin Transl Radiat Oncol, 2018 Mar 30; 8. PMID: 29594242    Free PMC article.
Impact of psychiatric illness on decreased survival in elderly patients with bladder cancer in the United States.
Usama Jazzar, Shan Yong, +10 authors, Stephen B Williams.
Cancer, 2018 Apr 17; 124(15). PMID: 29660813    Free PMC article.
Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment.
Victoria J Bray, Haryana M Dhillon, Janette L Vardy.
J Cancer Surviv, 2018 May 08; 12(4). PMID: 29728959
Systematic Review.
Efficacy of a hypnosis-based intervention to improve well-being during cancer: a comparison between prostate and breast cancer patients.
C Grégoire, H Nicolas, +6 authors, A Vanhaudenhuyse.
BMC Cancer, 2018 Jun 23; 18(1). PMID: 29929493    Free PMC article.
Gut microbiota-immune-brain interactions in chemotherapy-associated behavioral comorbidities.
Kelley R Jordan, Brett R Loman, Michael T Bailey, Leah M Pyter.
Cancer, 2018 Jul 06; 124(20). PMID: 29975400    Free PMC article.
Low Serum Carotenoids Are Associated with Self-Reported Cognitive Dysfunction and Inflammatory Markers in Breast Cancer Survivors.
Krystle E Zuniga, Nancy E Moran.
Nutrients, 2018 Aug 22; 10(8). PMID: 30126098    Free PMC article.
Diminished gray matter density mediates chemotherapy dosage-related cognitive impairment in breast cancer patients.
Xiu Li, Haijun Chen, +4 authors, Huaidong Cheng.
Sci Rep, 2018 Sep 16; 8(1). PMID: 30218006    Free PMC article.
Longitudinal Trajectory and Characterization of Cancer-Related Cognitive Impairment in a Nationwide Cohort Study.
Michelle C Janelsins, Charles E Heckler, +12 authors, Gary R Morrow.
J Clin Oncol, 2018 Sep 22;. PMID: 30240328    Free PMC article.
Cancer-related cognitive impairment in breast cancer survivors: An examination of conceptual and statistical cognitive domains using principal component analysis.
Maude Lambert, Lea Ann Ouimet, +4 authors, Catherine Bielajew.
Oncol Rev, 2018 Oct 09; 12(2). PMID: 30294410    Free PMC article.
Episodic memory for visual scenes suggests compensatory brain activity in breast cancer patients: a prospective longitudinal fMRI study.
Denise Pergolizzi, James C Root, +4 authors, Tim A Ahles.
Brain Imaging Behav, 2019 Jan 27; 13(6). PMID: 30680610    Free PMC article.
Understanding the Profile of Cancer-Related Cognitive Impairments: A Critique of Meta-Analyses.
Todd S Horowitz, Melissa Treviño, Ingrid M Gooch, Korrina A Duffy.
J Natl Cancer Inst, 2019 May 28; 111(10). PMID: 31127940    Free PMC article.
The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study.
Sheri J Hartman, Sandahl H Nelson, +3 authors, Ruth E Patterson.
Psychooncology, 2019 May 30; 28(8). PMID: 31140202    Free PMC article.
Cognitive performance of breast cancer survivors in daily life: Role of fatigue and depressed mood.
Brent J Small, Heather S L Jim, +2 authors, Stacey B Scott.
Psychooncology, 2019 Aug 17; 28(11). PMID: 31418499    Free PMC article.
Understanding on the association between informal caregiver characteristics and cognitive function of adults with cancer: a scoping review protocol.
Yesol Yang, Sharron Rushton, Amanda Woodward, Cristina Hendrix.
BMJ Open, 2019 Sep 21; 9(9). PMID: 31537575    Free PMC article.
Chemotherapy-Related Cognitive Impairment #342.
Katharine K Brewster, Daniel Shalev, Jon A Levenson.
J Palliat Med, 2017 Nov 02; 20(12). PMID: 29091520    Free PMC article.
MammaPrint guides treatment decisions in breast Cancer: results of the IMPACt trial.
Hatem Soliman, Varsha Shah, +11 authors, William Audeh.
BMC Cancer, 2020 Feb 02; 20(1). PMID: 32005181    Free PMC article.
Pupillary response: cognitive effort for breast cancer survivors.
Jamie S Myers, Melike Kahya, +10 authors, Hannes Devos.
Support Care Cancer, 2018 Aug 12; 27(3). PMID: 30097791    Free PMC article.
Impact of Breast Cancer Treatment on Employment: Results of a Multicenter Prospective Cohort Study (CANTO).
Agnes Dumas, Ines Vaz Luis, +18 authors, Gwenn Menvielle.
J Clin Oncol, 2019 Dec 14; 38(7). PMID: 31834818    Free PMC article.
Embracing the complexity: Older adults with cancer-related cognitive decline-A Young International Society of Geriatric Oncology position paper.
Mackenzi Pergolotti, Nicolò Matteo Luca Battisti, +12 authors, Tim A Ahles.
J Geriatr Oncol, 2019 Oct 18; 11(2). PMID: 31619372    Free PMC article.
Associations Between Breast Cancer Survivorship and Adverse Mental Health Outcomes: A Systematic Review.
Helena Carreira, Rachael Williams, +3 authors, Krishnan Bhaskaran.
J Natl Cancer Inst, 2018 Nov 08; 110(12). PMID: 30403799    Free PMC article.
Systematic Review.
Does walking protect against decline in cognitive functioning among breast cancer patients undergoing chemotherapy? Results from a small randomised controlled trial.
Kajal Gokal, Fehmidah Munir, +2 authors, Deborah Wallis.
PLoS One, 2018 Nov 30; 13(11). PMID: 30485297    Free PMC article.
Association of functional dorsal attention network alterations with breast cancer and chemotherapy.
Chao-Yu Shen, Vincent Chin-Hung Chen, +6 authors, Jun-Cheng Weng.
Sci Rep, 2019 Jan 16; 9(1). PMID: 30643203    Free PMC article.
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Trille Kristina Kjaer, Elisabeth Anne Wreford Andersen, +6 authors, Susanne Oksbjerg Dalton.
JAMA Oncol, 2019 Mar 08; 5(4). PMID: 30844031    Free PMC article.
Training Cognitive Functions Using Mobile Apps in Breast Cancer Patients: Systematic Review.
Laura Vergani, Giulia Marton, +3 authors, Gabriella Pravettoni.
JMIR Mhealth Uhealth, 2019 Mar 20; 7(3). PMID: 30888326    Free PMC article.
Systematic Review.
Exploring the Roles of Central and Peripheral Nervous System Function in Gait Stability: Preliminary Insights from Cancer Survivors.
Scott M Monfort, Xueliang Pan, +2 authors, Ajit M W Chaudhari.
Gait Posture, 2019 Apr 23; 71. PMID: 31009918    Free PMC article.
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Leslie Chang, Lauren S Weiner, +4 authors, Deborah M Kado.
J Geriatr Oncol, 2018 Aug 07; 10(2). PMID: 30078714    Free PMC article.
Cognitive performance in survivors of breast cancer and markers of biological aging.
Judith E Carroll, Kathleen Van Dyk, +5 authors, Patricia A Ganz.
Cancer, 2018 Nov 27; 125(2). PMID: 30474160    Free PMC article.
A mouse model of chemotherapy-related cognitive impairments integrating the risk factors of aging and APOE4 genotype.
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Behav Brain Res, 2020 Feb 07; 384. PMID: 32027870    Free PMC article.
Depression involved in self-reported prospective memory problems in survivors of breast cancer who have received chemotherapy.
Zhonglian Huang, Jingjing Zhao, +5 authors, Huaidong Cheng.
Medicine (Baltimore), 2019 Apr 23; 98(16). PMID: 31008981    Free PMC article.
Cognitive impairment after cytotoxic chemotherapy.
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Neurooncol Pract, 2020 Apr 08; 7(1). PMID: 32257280    Free PMC article.
Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial.
Ana Claudia Souza Palmer, Maxciel Zortea, +5 authors, Wolnei Caumo.
PLoS One, 2020 Apr 18; 15(4). PMID: 32302347    Free PMC article.
Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study.
Jeanne S Mandelblatt, Brent J Small, +23 authors, Tim Ahles.
J Clin Oncol, 2018 Oct 04;. PMID: 30281396    Free PMC article.
Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases.
Lien D Nguyen, Barbara E Ehrlich.
EMBO Mol Med, 2020 Apr 30; 12(6). PMID: 32346964    Free PMC article.
Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx.
Lynne I Wagner, Robert J Gray, +16 authors, David Cella.
J Clin Oncol, 2020 Apr 10; 38(17). PMID: 32271671    Free PMC article.
Cytokine-associated fatigue prior to, during, and post-chemotherapy for breast cancer.
R A Cohen, J M Gullett, +5 authors, D E Lyon.
J Neuroimmunol, 2019 Jul 02; 334. PMID: 31260949    Free PMC article.
A video-game based cognitive training for breast cancer survivors with cognitive impairment: A prospective randomized pilot trial.
Anne Bellens, Ella Roelant, +2 authors, Peter A van Dam.
Breast, 2020 Jun 20; 53. PMID: 32554133    Free PMC article.
Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial.
Jennifer Brunet, Meagan Barrett-Bernstein, +12 authors, Kristin L Campbell.
BMC Cancer, 2020 Aug 02; 20(1). PMID: 32736542    Free PMC article.
Modulation of Interhemispheric Functional Coordination in Breast Cancer Patients Receiving Chemotherapy.
Longxiang Tao, Lu Wang, +5 authors, Yongqiang Yu.
Front Psychol, 2020 Aug 28; 11. PMID: 32849022    Free PMC article.
Verbal Learning and Memory Function and the Influencing Factors on Breast Cancer Survivors: A Cross-Sectional Study.
Hilman Syarif, Agung Hilman Waluyo, Yati Afiyanti, Muchtaruddin Mansyur.
Asian Pac Isl Nurs J, 2019 Jul 02; 4(2). PMID: 31259233    Free PMC article.
Continuous, objective measurement of physical activity during chemotherapy for breast cancer: the Activity in Treatment pilot study.
Sandahl H Nelson, Lauren S Weiner, +3 authors, Sheri J Hartman.
Transl Behav Med, 2019 May 30; 10(4). PMID: 31141593    Free PMC article.
Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.
Wen Li, Jingjing Zhao, +4 authors, Li Shen.
Med Sci Monit, 2020 Sep 29; 26. PMID: 32985495    Free PMC article.
Neuroprotective effect of Mulmina™ against chemotherapy-induced cognitive decline in normal mice.
Manas Kinra, Niraja Ranadive, +6 authors, Krishnadas Nandakumar.
Biomed Rep, 2020 Nov 26; 14(1). PMID: 33235718    Free PMC article.
Longitudinal change of quality of life in the first five years of survival among disease-free Chinese breast cancer survivors.
Yuan-Yuan Lei, Suzanne C Ho, +5 authors, Winnie Yeo.
Qual Life Res, 2021 Jan 16; 30(6). PMID: 33447955
Role of inflammatory, oxidative, and ER stress signaling in the neuroprotective effect of atorvastatin against doxorubicin-induced cognitive impairment in rats.
Noha M Mounier, Sara A Wahdan, Amany M Gad, Samar S Azab.
Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar 24;. PMID: 33755739
Effects of acupuncture versus cognitive behavioral therapy on cognitive function in cancer survivors with insomnia: A secondary analysis of a randomized clinical trial.
Kevin T Liou, James C Root, +6 authors, Jun J Mao.
Cancer, 2020 Apr 23; 126(13). PMID: 32320061    Free PMC article.
A randomized trial of physical activity for cognitive functioning in breast cancer survivors: Rationale and study design of I Can! Improving Cognition After Cancer.
Sheri J Hartman, Lauren S Weiner, +6 authors, Kaylene Au.
Contemp Clin Trials, 2021 Jan 28; 102. PMID: 33503496    Free PMC article.
Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group.
Samantha J Mayo, Maryam Lustberg, +21 authors, Katherine B Peters.
Support Care Cancer, 2020 Nov 25; 29(6). PMID: 33231809
Cognitive Effects and Depression Associated With Taxane-Based Chemotherapy in Breast Cancer Survivors: A Meta-Analysis.
Eiman Y Ibrahim, Ilaria Domenicano, +4 authors, Barbara E Ehrlich.
Front Oncol, 2021 May 18; 11. PMID: 33996556    Free PMC article.
Systematic Review.