Skip to main content

The Effects of Breast Cancer Treatments on Cognition

  • Chapter
  • First Online:
Breast Cancer Survivorship

Abstract

There is growing concern among patients with early-stage breast cancer about self-perceived or objective cognitive changes following their diagnosis and treatment. Symptoms include difficulties with multi-tasking, short-term memory, attention and concentration and word-finding, which may have a detrimental effect on quality of life. The severity of symptoms varies widely, when assessed objectively, the problems are generally subtle. Early clinical observational studies accumulated evidence that suggested cognitive problems could be attributed to the direct neurotoxic effects of chemotherapy. However, observations of cognitive deficits before the start of any treatment question the singular role of chemotherapy. Additionally, results from studies examining the effect of endocrine therapies on cognitive function are mixed.

Recent neuroimaging techniques have reported structural and functional neural changes associated with breast cancer treatments. Also, translational research has accumulated evidence for the role of immune dysregulation and neurotoxicity from (pro-) inflammatory cytokines. It is clear that cognitive changes associated with breast cancer and its treatment are still far from being fully understood. Other contributing factors such as surgery, radiotherapy, the psychological burden of having cancer treatment, and treatment-related side effects, in particular fatigue may all play a role. Research into pharmacological and non-pharmacological interventions for cognitive impairment is in preliminary stages. Cognitive impairment following breast cancer diagnosis and treatment remains an important priority in breast cancer survivorship. Further investigations are needed to better understand symptoms and processes involved to enable the development of appropriate support for patients and survivors.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Janelsins MC, Kesler SR, Ahles TA, et al. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102–13.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Oxman TE, Silberfarb PM. Serial cognitive testing in cancer patients receiving chemotherapy. Am J Psychiatry. 1980;137:1263–5.

    Article  CAS  PubMed  Google Scholar 

  3. Wieneke MH, Dienst E. Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psycho Oncol. 1995;4:61–6.

    Article  Google Scholar 

  4. Van Dam FS, Schagen SB, Mueller MJ, et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst. 1998;90:210–8.

    Article  PubMed  Google Scholar 

  5. Ahles TA, Saykin AJ, Furstenberg CT, et al. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol. 2002;20:485–93.

    Article  CAS  PubMed  Google Scholar 

  6. Janelsins MC, Kohli S, Mohile SG, et al. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38:431–8.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ahles TA. Brain vulnerability to chemotherapy toxicities. Psycho Oncol. 2012;21:1141–8.

    Article  Google Scholar 

  8. Falleti MG, Sanfilippo A, Maruff P, 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. Brain Cogn. 2005;59:60–70.

    Article  PubMed  Google Scholar 

  9. Stewart A, Bielajew C, Collins B, et al. A meta-analysis of the neuropsychological effects of adjuvant chemotherapy treatment in women treated for breast cancer. Clin Neuropsychol. 2006;20:76–89.

    Article  PubMed  Google Scholar 

  10. Jim HS, Phillips KM, Chait S, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. J Clin Oncol. 2012;30:3578–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ono M, Ogilvie JM, Wilson JS, et al. A meta-analysis of cognitive impairment and decline associated with adjuvant chemotherapy in women with breast cancer. Front Oncol. 2015;5:59. doi:10.3389/fonc.2015.00059.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wefel JS, Lenzi R, Theriault RL, et al. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer. 2004;100:2292–9.

    Article  CAS  PubMed  Google Scholar 

  13. Collins B, Mackenzie J, Tasca GA, et al. Cognitive effects of chemotherapy in breast cancer patients: a dose–response study. Psycho Oncol. 2013;22:1517–27.

    Article  Google Scholar 

  14. Ahles TA, Saykin AJ. Breast cancer chemotherapy-related cognitive dysfunction. Clin Breast Cancer. 2002;3:S84–90.

    Article  CAS  PubMed  Google Scholar 

  15. Vearncombe KJ, Rolfe M, Wright M, et al. Predictors of cognitive decline after chemotherapy in breast cancer patients. J Int Neuropsychol Soc. 2009;15:951–62.

    Article  PubMed  Google Scholar 

  16. Mehlsen M, Pedersen AD, Jensen AB, et al. No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy. Psycho Oncol. 2009;18:248–57.

    Article  Google Scholar 

  17. Debess J, Riis JØ, Engebjerg MC, et al. Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Res Treat. 2010;121:91–100.

    Article  CAS  PubMed  Google Scholar 

  18. Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer. 2006;94:828–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ahles TA, Saykin AJ, McDonald BC, et al. Cognitive function in breast cancer patients prior to adjuvant treatment. Breast Cancer Res Treat. 2008;110:143–52.

    Article  CAS  PubMed  Google Scholar 

  20. Schilder CM, Seynaeve CM, Linn SC, et al. Cognitive functioning of postmenopausal breast cancer patients before adjuvant systemic therapy, and its association with medical and psychological factors. Crit Rev Oncol Hematol. 2010;76:133–41.

    Article  CAS  PubMed  Google Scholar 

  21. Cheung YT, Shwe M, Chui WK, et al. Effects of chemotherapy and psychosocial distress on perceived cognitive disturbances in Asian breast cancer patients. Ann Pharmacother. 2012;46:1645–55.

    Article  PubMed  Google Scholar 

  22. Reid-Arndt SA, Cox CR. Stress, coping and cognitive deficits in women after surgery for breast cancer. J Clin Psychol Med Settings. 2012;19:127–37.

    Article  PubMed  Google Scholar 

  23. Hermelink K, Untch M, Lux MP, et al. Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer. 2007;109:1905–13.

    Article  CAS  PubMed  Google Scholar 

  24. Zheng Y, Luo J, Bao P, et al. Long-term cognitive function change among breast cancer survivors. Breast Cancer Res Treat. 2014;146:599–609.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yamada TH, Denburg NL, Beglinger LJ, et al. Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. J Neuropsychiatry Clin Neurosci. 2010;22:48–54.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Koppelmans V, de Ruiter MB, van der Lijn F, et al. Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy. Breast Cancer Res Treat. 2012;132:1099–106.

    Article  CAS  PubMed  Google Scholar 

  27. Amidi A, Christensen S, Mehlsen M, et al. Long-term subjective cognitive functioning following adjuvant systemic treatment: 7–9 years follow-up of a nationwide cohort of women treated for primary breast cancer. Br J Cancer. 2015;113:794–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Broadbent DE, Cooper PF, FitzGerald P, et al. The Cognitive Failures Questionnaire (CFQ) and its correlates. Br J Clin Psychol. 1982;21:1–16.

    Article  PubMed  Google Scholar 

  29. Hutchinson AD, Hosking JR, Kichenadasse G, et al. Objective and subjective cognitive impairment following chemotherapy for cancer: a systematic review. Cancer Treat Rev. 2012;38:926–34.

    Article  PubMed  Google Scholar 

  30. Boykoff N, Moieni M, Subramanian SK. Confronting chemobrain: an in-depth look at survivors’ report of impact on work, social networks and health care response. J Cancer Surviv. 2009;3:223–32.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Von Ah D, Habermann B, Carpenter JS, et al. Impact of perceived cognitive impairment in breast cancer survivors. Eur J Oncol Nursing. 2013;17:236–41.

    Google Scholar 

  32. Player L, Mackenzie L, Willis K, et al. Women’s experiences of cognitive changes or ‘chemobrain’ following treatment for breast cancer: a role for occupational therapy? Aust Occup Ther J. 2014;61:230–40.

    Article  PubMed  Google Scholar 

  33. Ferguson RJ, McDonald BC, Saykin AJ, et al. Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol. 2007;25:3866–70.

    Article  PubMed  PubMed Central  Google Scholar 

  34. McDonald BC, Conroy SK, Ahles TA. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat. 2010;123:819–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. McDonald BC, Conroy SK, Smith DJ, et al. Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: a replication and extension study. Brain Behav Immun. 2013;30:S117–25.

    Article  PubMed  Google Scholar 

  36. Cheung YT, Ng T, Shwe M, et al. Association of pro-inflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study. Ann Oncol. 2015. doi:10.1093/annonc/mdv206.

    Google Scholar 

  37. Simó M, Rifà-Ros X, Rodriguez-Fornells A, et al. Chemobrain: a systematic review of structural and functional neuroimaging studies. Neuroscience Biobehav Rev. 2013;37:1311–21.

    Article  Google Scholar 

  38. Koppelmans V, Groot MD, de Ruiter MB, et al. Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy. Hum Brain Mapp. 2014;35:889–99.

    Article  PubMed  Google Scholar 

  39. Deprez S, Billiet T, Sunaert S, et al. Diffusion tensor MRI of chemotherapy-induced cognitive impairment in non-CNS cancer patients: a review. Brain Imaging Behav. 2013;7:409–35.

    Article  PubMed  Google Scholar 

  40. Deprez S, Amant F, Smeets A, et al. Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol. 2012;30:274–81.

    Article  PubMed  Google Scholar 

  41. Kesler S, Janelsins M, Koovakkattu D, et al. Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav Immun. 2013;30:S109–16.

    Article  CAS  PubMed  Google Scholar 

  42. Lopez Zunini RA, Scherling C, Wallis N, et al. Differences in verbal memory retrieval in breast cancer chemotherapy patients compared to healthy controls: a prospective fMRI study. Brain Imaging Behav. 2013;7:460–77.

    Article  PubMed  Google Scholar 

  43. Menning S, de Ruiter MB, Veltman DJ, et al. Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment-the role of fatigue. Neuroimage Clin. 2015;7:547–54.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Janelsins MC, Mustian KM, Palesh OG, et al. Differential expression of cytokines in BCS receiving different chemotherapies: implications for cognitive impairment research. Support Care Cancer. 2012;20:831–9.

    Article  PubMed  Google Scholar 

  45. Ganz PA, Bower JE, Kwan L, et al. Does tumor necrosis factor-alpha (TNF-α) play a role in post-chemotherapy cerebral dysfunction? Brain Behav Immun. 2013;30:S99–108.

    Article  CAS  PubMed  Google Scholar 

  46. Tsavaris N, Kosmas C, Vadiaka M, et al. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer. 2002;87:21–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pomykala KL, Ganz PA, Bower JE, et al. The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer. Brain Imaging Behav. 2013;7:511–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mills PJ, Ancoli-Israel S, Parker B, et al. Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer. Brain Behav Immun. 2008;22:98–104.

    Article  CAS  PubMed  Google Scholar 

  49. Squire L. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992;99:195–231.

    Article  CAS  PubMed  Google Scholar 

  50. Alves S, McEwen B. Estrogen and brain function: implications for aging and dementia. New York: Springer; 1999.

    Google Scholar 

  51. Roselli CE, Klosterman SA, Fasasi TA. Sex differences in androgen responsiveness in the rat brain: regional differences in the induction of aromatase activity. Neuroendocrinology. 1996;64:139–45.

    Article  CAS  PubMed  Google Scholar 

  52. Breuer B, Anderson R. The relationship of tamoxifen with dementia, depression and dependence in activities of daily living in elderly nursing home residents. Women Health. 2000;31:71–85.

    Article  CAS  PubMed  Google Scholar 

  53. Ernst T, Chang L, Cooray D, et al. The effects of tamoxifen andestrogen on brain metabolism in elderly women. J Natl Cancer Inst. 2002;94:592–7.

    Article  CAS  PubMed  Google Scholar 

  54. Bender CM, Sereika SM, Brufsky AM, et al. Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer. Menopause. 2007;14:995–8.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Boele FW, Schilder CMT, De Roode ML, et al. Cognitive functioning during long-term tamoxifen treatment in postmenopausal women with breast cancer. Menopause. 2015;22:17–25.

    Article  PubMed  Google Scholar 

  56. Jenkins V, Shilling V, Fallowfield L, et al. Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. Psycho Oncol. 2004;13:61–6.

    Article  Google Scholar 

  57. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371–88.

    Article  CAS  PubMed  Google Scholar 

  58. Schilder CM, Eggens PC, Seynaeve C, et al. Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol. 2009;48:76–85.

    Article  CAS  PubMed  Google Scholar 

  59. Phillips K, Aldridge J, Ribi K, et al. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1–98 trial. Breast Cancer Res Treatment. 2011;126:221–6.

    Article  CAS  Google Scholar 

  60. Jenkins VA, Ambroisine LM, Atkins L, et al. Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet Oncol. 2008;9:953–61.

    Article  CAS  PubMed  Google Scholar 

  61. Chan RJ, McCarthy AL, Devenish J, et al. Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer. Eur J Cancer. 2015;51:437–50.

    Article  CAS  PubMed  Google Scholar 

  62. Davis J, Ahlberg FM, Berk M, et al. Emerging pharmacotherapy for cancer patients with cognitive dysfunction. BMC Neurol. 2013;13:153.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dolbeault S, Cayrou S, Brédart A. The effectiveness of a psycho-educational group after early-stage breast cancer treatment: results of a randomized French study. Psych Oncol. 2009;18:647–56.

    Article  CAS  Google Scholar 

  64. Ferguson RJ, McDonald BC, Rocque MA, et al. Development of CBT for chemotherapy-related cognitive change: Results of a waitlist control trial. Psycho Oncol. 2012;21:176–86.

    Article  Google Scholar 

  65. Von Ah D, Carpenter JS, Saykin A, et al. Advanced cognitive training for breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat. 2012;135:799–809.

    Article  Google Scholar 

  66. Kesler SR, Hadi Hosseini SM, Heckler C, et al. Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer. 2013;13:299–306.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Ercoli LM, Petersen L, Hunter AM, et al. Cognitive rehabilitation group intervention for breast cancer survivors: results of a randomized clinical trial. Psycho Oncol. 2015;24:1360–7.

    Article  CAS  Google Scholar 

  68. Damholdt MF, Mehlsen M, O’Toole MS, et al. Web-based cognitive training for breast cancer survivors with cognitive complaints – a randomized controlled trial. Psych Oncol. 2016. doi:10.1002/pon.4058.

    Google Scholar 

  69. Alvarez J, Meyer FL, Granoff DL, et al. The effect of EEG biofeedback on reducing postcancer cognitive impairment. Integr Cancer Ther. 2013;12:475–87.

    Article  PubMed  Google Scholar 

  70. Johns SA, Von Ah D, Brown LF. Randomized controlled pilot trial of mindfulness-based stress reduction for breast and colorectal cancer survivors: effects on cancer-related cognitive impairment. J Cancer Surviv. 2016;10:437–48. doi:10.1007/s11764-015-0494-3.

    Google Scholar 

  71. Derry HM, Jaremka LM, Bennet JM, et al. Yoga and self-reported cognitive problems in breast cancer survivors: a randomized controlled trial. Psycho Oncol. 2015;24:958–66.

    Article  Google Scholar 

  72. Wefel JS, Vardy J, Ahles T, et al. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12:703–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Helena Harder PhD, MSc, BSc .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Harder, H., Jenkins, V. (2016). The Effects of Breast Cancer Treatments on Cognition. In: Ring, A., Parton, M. (eds) Breast Cancer Survivorship. Springer, Cham. https://doi.org/10.1007/978-3-319-41858-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-41858-2_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-41856-8

  • Online ISBN: 978-3-319-41858-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics