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

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.

[1]  Andrew J Saykin,et al.  Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Andrew J Saykin,et al.  Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  S. Sereika,et al.  Cognitive impairment associated with adjuvant therapy in breast cancer , 2006, Psycho-oncology.

[4]  M. Lezak,et al.  Neuropsychological assessment, 4th ed. , 2004 .

[5]  V. Shilling,et al.  Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer. , 2007, European journal of oncology nursing : the official journal of European Oncology Nursing Society.

[6]  B. Collins Acute and Late Onset Cognitive Dysfunction Associated With Chemotherapy in Women With Breast Cancer: Wefel JS, Saleeba AK, Buzdar AU, et al (The Univ of Texas M D Anderson Cancer Ctr, Houston) Cancer 116:3348-3356, 2010 , 2011 .

[7]  M. Muller,et al.  Neurophysiological Evaluation of Late Effects of Adjuvant High-dose Chemotherapy on Cognitive Function , 2004, Journal of Neuro-Oncology.

[8]  Paul Maruff,et al.  The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: A meta-analysis of the current literature , 2005, Brain and Cognition.

[9]  Catechol‐O‐Methyltransferase Genotype Modulates Opioid Release in Decision Circuitry , 2013, Clinical and translational science.

[10]  C. Gundy,et al.  Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  D. Grosshans,et al.  Catechol-O-Methyltransferase Genotype Modulates Cancer Treatment-Related Cognitive Deficits in Breast Cancer Survivors: Small BJ, Rawson KS, Walsh E, et al (Univ of South Florida, Tampa, FL; Univ of Kentucky College of Medicine, Lexington; et al) Cancer 117:1369-1376, 2011§ , 2011 .

[12]  N. Hanna,et al.  Is"chemobrain" a transient state? A prospective pilot study among persons with non-small cell lung cancer. , 2008, The journal of supportive oncology.

[13]  M. Muller,et al.  Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. , 2006, Journal of the National Cancer Institute.

[14]  L. Hedges,et al.  Introduction to Meta‐Analysis , 2009, International Coaching Psychology Review.

[15]  M Abdolell,et al.  Cognitive function in breast cancer patients receiving adjuvant chemotherapy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  S. Rodenhuis,et al.  Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. , 1998, Journal of the National Cancer Institute.

[17]  M. Lux,et al.  Short‐term effects of treatment‐induced hormonal changes on cognitive function in breast cancer patients , 2008, Cancer.

[18]  R. Orwin A fail-safe N for effect size in meta-analysis. , 1983 .

[19]  H. Jim,et al.  Cognitive functioning in breast cancer survivors: A controlled comparison , 2009, Cancer.

[20]  A. Saykin,et al.  The relationship of APOE genotype to neuropsychological performance in long‐term cancer survivors treated with standard dose chemotherapy , 2003, Psycho-oncology.

[21]  C. Bielajew,et al.  A Meta-Analysis of the Neuropsychological Effects of Adjuvant Chemotherapy Treatment in Women Treated for Breast Cancer , 2006, The Clinical neuropsychologist.

[22]  L. Hedges,et al.  Statistical Methods for Meta-Analysis , 1987 .

[23]  Uwe Koch,et al.  The association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life in breast cancer survivors following standard adjuvant versus high-dose chemotherapy. , 2007, Patient education and counseling.

[24]  Frank Baker,et al.  Adult cancer survivors: How are they faring? , 2005, Cancer.

[25]  K. Ball,et al.  Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial. , 2010, European journal of cancer care.

[26]  T. Nakano,et al.  No adverse effects of adjuvant chemotherapy on hippocampal volumein Japanese breast cancer survivors , 2005, Breast Cancer Research and Treatment.

[27]  D. Veltman,et al.  Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer , 2011, Human brain mapping.

[28]  T. Delozier,et al.  [Renal carcinoma and fatigue: which challenge in the era of antiangiogenic drugs?]. , 2011, Bulletin du cancer.

[29]  Bruce E Compas,et al.  Neuropsychological effects of treatments for adults with cancer: A meta-analysis and review of the literature , 2003, Journal of the International Neuropsychological Society.

[30]  P. Jacobsen,et al.  Cognitive functioning after adjuvant chemotherapy and/or radiotherapy for early‐stage breast carcinoma , 2005, Cancer.

[31]  Robert G. Orwin,et al.  A Fail-SafeN for Effect Size in Meta-Analysis , 1983 .

[32]  E. Venkatraman,et al.  Phase I/II study of weekly paclitaxel plus carboplatin and gemcitabine as first-line treatment of advanced-stage ovarian cancer: pathologic complete response and longitudinal assessment of impact on cognitive functioning. , 2006, Gynecologic oncology.

[33]  Juan Carlos Espinosa,et al.  Comprehensive Meta-Analysis , 2004 .

[34]  S. Mohile,et al.  An update on cancer- and chemotherapy-related cognitive dysfunction: current status. , 2011, Seminars in oncology.

[35]  M. El-Tamer,et al.  The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study , 2010, Breast Cancer Research and Treatment.

[36]  H. Jim,et al.  Catechol‐O‐methyltransferase genotype modulates cancer treatment‐related cognitive deficits in breast cancer survivors , 2011, Cancer.

[37]  T. Ahles,et al.  International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. , 2011, The Lancet. Oncology.

[38]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[39]  J. Holland,et al.  Cognitive Function of Older Patients Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Prospective Longitudinal Study , 2006, Journal of the American Geriatrics Society.

[40]  J. Ioannidis,et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. , 2009, Journal of clinical epidemiology.

[41]  M. Muller,et al.  Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma , 1999, Cancer.

[42]  S. Allan,et al.  A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer , 2006, British Journal of Cancer.

[43]  M. Dodd,et al.  A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients , 2011, Supportive Care in Cancer.

[44]  L. Carlson,et al.  Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls , 2008, Journal of cancer survivorship : research and practice.

[45]  I. Tannock,et al.  Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  K. Hermelink Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer , 2011, Cancer.

[47]  S. Schultz,et al.  Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. , 2010, The Journal of neuropsychiatry and clinical neurosciences.

[48]  S. Schagen,et al.  Does cognitive impairment after chemotherapy for breast cancer improve over time or does practice make perfect? , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  M. Mehlsen,et al.  Long-term cognitive function following chemotherapy in patients with testicular cancer , 2009, Journal of the International Neuropsychological Society.

[50]  G. Winocur,et al.  Chemotherapy and Cognitive Impairment: Treatment Options , 2011, Clinical pharmacology and therapeutics.

[51]  C. Bielajew,et al.  Cognitive effects of chemotherapy in post‐menopausal breast cancer patients 1 year after treatment , 2009, Psycho-oncology.

[52]  Michael E. Phelps,et al.  Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy , 2007, Breast Cancer Research and Treatment.

[53]  S. Fosså,et al.  Self-reported cognitive problems in testicular cancer patients: relation to neuropsychological performance, fatigue, and psychological distress. , 2011, Journal of psychosomatic research.

[54]  Joel Kramer,et al.  A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function , 2005, Cancer.

[55]  H. Jim,et al.  Cognitive functioning after cancer treatment , 2012, Cancer.

[56]  P. Sismondi,et al.  Effects of surgical and adjuvant therapies for breast cancer on sexuality, cognitive functions, and body weight. , 2010, The journal of sexual medicine.

[57]  A. Saykin,et al.  Cognitive‐behavioral management of chemotherapy‐related cognitive change , 2007, Psycho-oncology.

[58]  S. Rodenhuis,et al.  Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[59]  E. Thiel,et al.  Neuropsychological function in high-risk breast cancer survivors after stem-cell supported high-dose therapy versus standard-dose chemotherapy: evaluation of long-term treatment effects. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[60]  M. Muller,et al.  Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer , 2008, Acta oncologica.

[61]  I. Tannock,et al.  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. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  P. Ganz,et al.  Neurocognitive Performance in Breast Cancer Survivors Exposed to Adjuvant Chemotherapy and Tamoxifen , 2004, Journal of clinical and experimental neuropsychology.

[63]  C. Bielajew,et al.  Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study , 2009, Psycho-oncology.

[64]  Yutaka Matsuoka,et al.  Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy , 2007, Cancer.

[65]  R. Tweedie,et al.  A Nonparametric “Trim and Fill” Method of Accounting for Publication Bias in Meta-Analysis , 2000 .