Skip to main content

Advertisement

Log in

Cognitive function and breast cancer: promise and potential insights from functional brain imaging

  • Invited Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Altered cognitive function can be a distressing side effect of cancer and its treatment. Women diagnosed and treated for breast cancer often report problems with memory, concentration, and other cognitive abilities that can pose significant barriers to full resumption of family, job, and social roles. Despite considerable neuropsychological research, many unanswered questions remain about cancer-related cognitive deficits and the underlying neural bases. Functional magnetic resonance imaging (fMRI) measures brain activation associated with different mental states and has significantly advanced our understanding of cognitive function and dysfunction in healthy and clinical populations. However, to date the application of fMRI to the study of cognitive function in breast cancer is limited. The current review addresses the potential importance of this method for understanding the neurocognitive effects of breast cancer disease and treatment. Along with reviewing published fMRI studies on breast cancer to date, we discuss potential major contributions of this method which include: (a) delineating components of cognitive function and underlying neural processes most affected by cancer and its treatment, (b) uncovering compensatory processes and their limits, (c) identifying altered resting state networks that may relate to subjective complaints and longer term outcomes, and (d) clarifying the relationship between pre-treatment alterations in brain activity and longer term neural and behavioral outcomes. Finally, we pose questions for future research that can be optimally addressed by integrating fMRI and other imaging modalities to clarify the nature and causes of “chemo brain” and guide interventions to improve cognitive function and the quality of breast cancer survivorship.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. American Cancer Society (2012) Breast cancer facts and figures 2011–2012. American Cancer Society Inc., Atlanta

    Google Scholar 

  2. Trudeau M, Charbonneau F, Gelmon K, Laing K, Latreille J, Mackey J, McLeod D, Pritchard K, Provencher L, Verma S (2005) Selection of adjuvant chemotherapy for treatment of node-positive breast cancer. Lancet Oncol 6(11):886–898

    Article  PubMed  CAS  Google Scholar 

  3. Boykoff N, Moieni M, Subramanian SK (2009) Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 3(4):223–232

    Article  PubMed  Google Scholar 

  4. Wefel JS, Schagen SB (2012) Chemotherapy-related cognitive dysfunction. Curr Neurol Neurosci Rep 12(3):267–275

    Article  PubMed  CAS  Google Scholar 

  5. Wefel JS, Vardy J, Ahles T, Schagen SB (2011) International cognition and cancer task force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12(7):703–708

    Article  PubMed  Google Scholar 

  6. Ahles TA, Saykin A (2001) Cognitive effects of standard-dose chemotherapy in patients with cancer. Cancer Invest 19(8):812–820

    Article  PubMed  CAS  Google Scholar 

  7. Anderson-Hanley C, Sherman ML, Riggs R, Agocha VB, Compas BE (2003) Neuropsychological effects of treatments for adults with cancer: a meta-analysis and review of the literature. J Int Neuropsychol Soc 9(7):967–982

    Article  PubMed  Google Scholar 

  8. Castellon SA, Silverman DH, Ganz PA (2005) Breast cancer treatment and cognitive functioning: current status and future challenges in assessment. Breast Cancer Res Treat 92(3):199–206

    Article  PubMed  Google Scholar 

  9. Tannock IF, Ahles TA, Ganz PA, Van Dam FS (2004) Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 22(11):2233–2239

    Article  PubMed  Google Scholar 

  10. Ahles TA, Saykin AJ, McDonald BC, Furstenberg CT, Cole BF, Hanscom BS, Mulrooney TJ, Schwartz GN, Kaufman PA (2008) Cognitive function in breast cancer patients prior to adjuvant treatment. Breast Cancer Res Treat 110(1):143–152

    Article  PubMed  CAS  Google Scholar 

  11. Hermelink K, Untch M, Lux MP, Kreienberg R, Beck T, Bauerfeind I, Munzel K (2007) Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer 109(9):1905–1913

    Article  PubMed  CAS  Google Scholar 

  12. Hedayati E, Schedin A, Nyman H, Alinaghizadeh H, Albertsson M (2011) The effects of breast cancer diagnosis and surgery on cognitive functions. Acta Oncol 50(7):1027–1036

    Article  PubMed  Google Scholar 

  13. Hurria A, Rosen C, Hudis C, Zuckerman E, Panageas KS, Lachs MS, Witmer M, van Gorp WG, Fornier M, D’Andrea G, Moasser M, Dang C, Van Poznak C, Holland J (2006) Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc 54(6):925–931

    Article  PubMed  Google Scholar 

  14. Shilling V, Jenkins V, Morris R, Deutsch G, Bloomfield D (2005) The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study. Breast 14(2):142–150

    Article  PubMed  CAS  Google Scholar 

  15. Tager FA, McKinley PS, Schnabel FR, El-Tamer M, Cheung YK, Fang Y, Golden CR, Frosch ME, Habif U, Mulligan MM, Chen IS, Hershman DL (2010) The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study. Breast Cancer Res Treat 123(1):25–34

    Article  PubMed  Google Scholar 

  16. Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA (2004) The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer 100(11):2292–2299

    Article  PubMed  CAS  Google Scholar 

  17. Wefel JS, Saleeba AK, Buzdar AU, Meyers CA (2010) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 116(14):3348–3356

    Article  PubMed  Google Scholar 

  18. Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS, Mulrooney TJ, Schwartz GN, Kaufman PA (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 28(29):4434–4440

    Article  PubMed  Google Scholar 

  19. Stern Y (2009) Cognitive reserve. Neuropsychologia 47(10):2015–2028

    Article  PubMed  Google Scholar 

  20. Jansen CE, Cooper BA, Dodd MJ, Miaskowski CA (2011) A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Support Care Cancer 19(10):1647–1656

    Article  PubMed  Google Scholar 

  21. Jenkins V, Shilling V, Deutsch G, Bloomfield D, Morris R, Allan S, Bishop H, Hodson N, Mitra S, Sadler G, Shah E, Stein R, Whitehead S, Winstanley J (2006) A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 94(6):828–834

    Article  PubMed  CAS  Google Scholar 

  22. Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB (2012) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30(10):1080–1086

    Article  PubMed  Google Scholar 

  23. Huettel SA, Song AW, McCarthy G (2009) Functional magnetic resonance imaging, 2nd edn. Sinauer Associates, Sunderland, MA

    Google Scholar 

  24. Poldrack RA, Mumford JA, Nichols TE (2011) Handbook of functional MRI data analysis. Cambridge University Press, New York, NY

    Book  Google Scholar 

  25. Poldrack RA (2007) Region of interest analysis for fMRI. Soc Cogn Affect Neurosci 2(1):67–70

    Article  PubMed  Google Scholar 

  26. Reuter-Lorenz PA, Lustig C (2005) Brain aging: reorganizing discoveries about the aging mind. Curr Opin Neurobiol 15(2):245–251

    Article  PubMed  CAS  Google Scholar 

  27. Yarkoni T, Poldrack RA, Van Essen DC, Wager TD (2010) Cognitive neuroscience 2.0: building a cumulative science of human brain function. Trends Cogn Sci 14(11):489–496

    Article  PubMed  Google Scholar 

  28. Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453(7197):869–878

    Article  PubMed  CAS  Google Scholar 

  29. Schleim S, Roiser JP (2009) FMRI in translation: the challenges facing real-world applications. Frontiers Hum Neurosci 3:63

    Google Scholar 

  30. D’ Esposito M (2006) Functional MRI: applications in clinical neurology and psychiatry. Taylor and Francis, New York

    Google Scholar 

  31. Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Frontiers Syst Neurosci 4:19

    Google Scholar 

  32. Jonides J, Lewis RL, Nee DE, Lustig CA, Berman MG, Moore KS (2008) The mind and brain of short-term memory. Annu Rev Psychol 59:193–224

    Article  PubMed  Google Scholar 

  33. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ, Boven E, Schagen SB (2011) Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp 32(8):1206–1219

    Article  PubMed  Google Scholar 

  34. Kesler SR, Kent JS, O’Hara R (2011) Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol 68(11):1447–1453

    Article  PubMed  Google Scholar 

  35. Kesler SR, Bennett FC, Mahaffey ML, Spiegel D (2009) Regional brain activation during verbal declarative memory in metastatic breast cancer. Clin Cancer Res 15(21):6665–6673

    Article  PubMed  CAS  Google Scholar 

  36. Mattay VS, Goldberg TE (2004) Imaging genetic influences in human brain function. Curr Opin Neurobiol 14(2):239–247

    Article  PubMed  CAS  Google Scholar 

  37. Raemaekers M, Ramsey NF, Vink M, van den Heuvel MP, Kahn RS (2006) Brain activation during antisaccades in unaffected relatives of schizophrenic patients. Biol Psychiatry 59(6):530–535

    Article  PubMed  Google Scholar 

  38. Dumontheil I, Klingberg T (2011) Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later. Cereb Cortex 22(5):1078–1085

    Google Scholar 

  39. Yang Z, Yeo RA, Pena A, Ling JM, Klimaj S, Campbell R, Doezema D, Mayer AR (2012) An fMRI study of auditory orienting and inhibition of return in pediatric mild traumatic brain injury. J Neurotrauma. doi:10.1089/neu.2012.2395

    Google Scholar 

  40. Reuter-Lorenz PA, Cappell KA (2008) Neurocognitive aging and the compensation hypothesis. Curr Dir Psychol Sci 17(3):177–182

    Article  Google Scholar 

  41. Ferguson RJ, McDonald BC, Saykin AJ, Ahles TA (2007) Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol 25(25):3866–3870

    Article  PubMed  Google Scholar 

  42. Schneider-Garces NJ, Gordon BA, Brumback-Peltz CR, Shin E, Lee Y, Sutton BP, Maclin EL, Gratton G, Fabiani M (2010) Span, CRUNCH, and beyond: working memory capacity and the aging brain. J Cogn Neurosci 22(4):655–669

    Article  PubMed  Google Scholar 

  43. Cappell KA, Gmeindl L, Reuter-Lorenz PA (2010) Age differences in prefrontal recruitment during verbal working memory maintenance depend on memory load. Cortex 46(4):462–473

    Article  PubMed  Google Scholar 

  44. McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ (2012) Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study. J Clin Oncol 30(20):2500–2508

    Article  PubMed  Google Scholar 

  45. McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ (2010) Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 123(3):819–828

    Article  PubMed  CAS  Google Scholar 

  46. Biswal BB (2012) Resting state fMRI: a personal history. Neuroimage 62(2):938–944

    Article  PubMed  Google Scholar 

  47. Wang L, Zang Y, He Y, Liang M, Zhang X, Tian L, Wu T, Jiang T, Li K (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage 31(2):496–504

    Article  PubMed  Google Scholar 

  48. Tian L, Jiang T, Wang Y, Zang Y, He Y, Liang M, Sui M, Cao Q, Hu S, Peng M, Zhuo Y (2006) Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder. Neurosci Lett 400(1–2):39–43

    Article  PubMed  CAS  Google Scholar 

  49. Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C (2009) Abnormalities of intrinsic functional connectivity in autism spectrum disorders. Neuroimage 47(2):764–772

    Article  PubMed  Google Scholar 

  50. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38

    Article  PubMed  Google Scholar 

  51. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci USA 98(2):676–682

    Article  PubMed  CAS  Google Scholar 

  52. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102(27):9673–9678

    Article  PubMed  CAS  Google Scholar 

  53. Weissman DH, Roberts KC, Visscher KM, Woldorff MG (2006) The neural bases of momentary lapses in attention. Nat Neurosci 9(7):971–978

    Article  PubMed  CAS  Google Scholar 

  54. Berman MG, Peltier S, Nee DE, Kross E, Deldin PJ, Jonides J (2011) Depression, rumination and the default network. Soc Cogn Affect Neurosci 6(5):548–555

    Article  PubMed  Google Scholar 

  55. Smallwood J, Beach E, Schooler JW, Handy TC (2008) Going AWOL in the brain: mind wandering reduces cortical analysis of external events. J Cogn Neurosci 20(3):458–469

    Article  PubMed  Google Scholar 

  56. Buckner RL, Sepulcre J, Talukdar T, Krienen FM, Liu H, Hedden T, Andrews-Hanna JR, Sperling RA, Johnson KA (2009) Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer’s disease. J Neurosci 29(6):1860–1873

    Article  PubMed  CAS  Google Scholar 

  57. Cook DB, O’Connor PJ, Lange G, Steffener J (2007) Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage 36(1):108–122

    Article  PubMed  Google Scholar 

  58. Lim J, Wu WC, Wang J, Detre JA, Dinges DF, Rao H (2010) Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect. Neuroimage 49(4):3426–3435

    Article  PubMed  Google Scholar 

  59. Berger AM, Gerber LH, Mayer DK (2012) Cancer-related fatigue: implications for breast cancer survivors. Cancer 118(8 Suppl):2261–2269

    Article  PubMed  Google Scholar 

  60. Bruno J, Hosseini SM, Kesler S (2012) Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors. Neurobiol Dis. doi:10.1016/j.nbd.2012.07.009

    PubMed  Google Scholar 

  61. Cimprich B, Reuter-Lorenz P, Nelson J, Clark PM, Therrien B, Normolle D, Berman MG, Hayes DF, Noll DC, Peltier S, Welsh RC (2010) Prechemotherapy alterations in brain function in women with breast cancer. J Clin Exp Neuropsychol 32(3):324–331

    Article  PubMed  Google Scholar 

  62. Hedayati E, Alinaghizadeh H, Schedin A, Nyman H, Albertsson M (2012) Effects of adjuvant treatment on cognitive function in women with early breast cancer. Eur J Oncol Nurs 16(3):315–322

    Article  PubMed  Google Scholar 

  63. Reid-Arndt SA, Hsieh C, Perry MC (2010) Neuropsychological functioning and quality of life during the first year after completing chemotherapy for breast cancer. Psychooncology 19(5):535–544

    Article  PubMed  Google Scholar 

  64. Vearncombe KJ, Rolfe M, Andrew B, Pachana NA, Wright M, Beadle G (2011) Cognitive effects of chemotherapy-induced menopause in breast cancer. Clin Neuropsychol 25(8):1295–1313

    Article  PubMed  Google Scholar 

  65. Scherling C, Collins B, Mackenzie J, Bielajew C, Smith A (2011) Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. Frontiers Hum Neurosci 5:122

    Google Scholar 

  66. Scherling C, Collins B, Mackenzie J, Bielajew C, Smith A (2012) Prechemotherapy differences in response inhibition in breast cancer patients compared to controls: a functional magnetic resonance imaging study. J Clin Exp Neuropsychol 34(5):543–560

    Article  PubMed  Google Scholar 

  67. Bennett CM, Miller MB (2010) How reliable are the results from functional magnetic resonance imaging? Ann N Y Acad Sci 1191:133–155

    Article  PubMed  Google Scholar 

  68. Nagel IE, Preuschhof C, Li SC, Nyberg L, Backman L, Lindenberger U, Heekeren HR (2009) Performance level modulates adult age differences in brain activation during spatial working memory. Proc Natl Acad Sci USA 106(52):22552–22557

    Article  PubMed  CAS  Google Scholar 

  69. Lane RD, Wager TD (2009) Introduction to a special issue of neuroimage on brain-body medicine. Neuroimage 47(3):781–784

    Article  PubMed  Google Scholar 

  70. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, Caan M, Douaud G, Lavini C, Linn SC, Boven E, van Dam FS, Schagen SB (2011) Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Hum Brain Mapp. doi:10.1002/hbm.21422

    Google Scholar 

Download references

Acknowledgments

We thank Mary K. Askren, Marc Berman, Lynn Ossher, Scott Peltier, and Barbara Therrien for their insightful feedback on an earlier version of this manuscript. We also thank MiSook Jung for her numerous valuable contributions to the preparation of this manuscript. The authors declare that they have no disclosures or conflicts of interest. Preparation of the manuscript was supported by NIH, NINR, R01 NRO 10939 (BC).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patricia A. Reuter-Lorenz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reuter-Lorenz, P.A., Cimprich, B. Cognitive function and breast cancer: promise and potential insights from functional brain imaging. Breast Cancer Res Treat 137, 33–43 (2013). https://doi.org/10.1007/s10549-012-2266-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-012-2266-3

Keywords

Navigation