Breast Cancer Research and Treatment

, Volume 123, Issue 1, pp 25–34 | Cite as

The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study

  • Felice A. Tager
  • Paula S. McKinley
  • Freya R. Schnabel
  • Mahmoud El-Tamer
  • Ying Keun K. Cheung
  • Yixin Fang
  • Claire R. Golden
  • Margery E. Frosch
  • Ulya Habif
  • Margaret M. Mulligan
  • Ivy S. Chen
  • Dawn L. Hershman
Preclinical study

Abstract

Studies suggest that adjuvant chemotherapy for early stage breast cancer (BC) is associated with cognitive impairment related to attention, memory, and visuospatial functioning. However, other studies have failed to confirm that relationship. We report one of the first longitudinal, controlled studies of cognitive effects of chemotherapy in older post-menopausal women. Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy (Time1), six months after treatment (Time2), and at a final 6-month follow-up (Time3). Thirty women were treated with chemotherapy; thirty-one women who received no chemotherapy were controls. Cognitive domains measured included motor, language, attention/concentration/working memory, visuospatial, and memory (verbal and visual). Time-by-treatment interaction was significant in the motor domain (P = 0.007) with poorer performance in women treated with chemotherapy. For the other domains, scores did not significantly vary over time by group. In post-menopausal women, chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors: attention, memory, and information processing. Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing. Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits.

Keywords

Breast cancer Chemotherapy Post-menopausal Cognitive function 

Supplementary material

10549_2009_606_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 kb)

References

  1. 1.
    Raffa RB, Duong PV, Finney J, Garber DA, Lam LM, Mathew SS, Patel NN, Plaskett KC, Shah M, Jen Weng HF (2006) Is ‘chemo-fog’/’chemo-brain’ caused by cancer chemotherapy? J Clin Pharm Ther 31(2):129–138CrossRefPubMedGoogle Scholar
  2. 2.
    Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, Whedon MB, Bivens S, Mitchell T, Greenberg ER et al (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 20(2):485–493CrossRefPubMedGoogle Scholar
  3. 3.
    Brezden CB, Phillips KA, Abdollel MTB, Tannock IF (2000) Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 18(14):2695–2701PubMedGoogle Scholar
  4. 4.
    Schagen SB, Van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF (1999) Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 85(3):640–650CrossRefPubMedGoogle Scholar
  5. 5.
    van Dam F, Schagen SB, Muller MJ, Boogerd W, vd Wall E, Fortuyn MED, Rodenhuis S (1998) Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: High dose versus standard-dose chemotherapy. J Natl Cancer Inst 90(3):210–218CrossRefPubMedGoogle Scholar
  6. 6.
    Wieneke MH, Dienst ER (1995) Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psychooncology 4(1):61–66CrossRefGoogle Scholar
  7. 7.
    Wefel JS, Lenzi R, Theriault RL, Buzdar AU, Cruickshank S, Meyers CA (2004) “Chemobrain” in breast carcinoma? A prologue. Cancer 101(3):466–475CrossRefPubMedGoogle Scholar
  8. 8.
    Jenkins V, Shilling V, Deutsch G, Bloomfield D, Morris R, Allan S, Bishop H, Hodson N, Mitra S, Sadler G et al (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):828–834CrossRefPubMedGoogle Scholar
  9. 9.
    Hurria A, Rosen C, Hudis C, Zuckerman E, Panageas KS, Lachs MS, Witmer M, van Gorp WG, Fornier M, D’Andrea G et al (2006) Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc 54(6):927–931CrossRefGoogle Scholar
  10. 10.
    Stewart A, Collins B, Mackenzie J, Tomiak E, Verma S, Bielajew C (2008) The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology 17:122–130CrossRefPubMedGoogle Scholar
  11. 11.
    Jansen CE, Miaskowski C, Dodd M, Dowling G, Kramer J (2005) A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function. Cancer 104(10):2222–2233CrossRefPubMedGoogle Scholar
  12. 12.
    Klove H (1963) Clinical neuropsychology. In: Forester F (ed) Medical clinics of North America. Saunders, New York City, NYGoogle Scholar
  13. 13.
    Matthews C, Klove H (1964) Instructional manual for the adult neuropsychological tests battery. University of Wisconsin Medical School, Madison, WIGoogle Scholar
  14. 14.
    Bornstein RA (1985) Normative data on selected neuropsychological measures from a non-clinical sample. J Clin Psychol 41(5):651–659CrossRefGoogle Scholar
  15. 15.
    Benton AL, Hamsher K, Sivan AB (1983) Multilingual aphasia examination, 3rd edn. AJA Associates, Iowa CityGoogle Scholar
  16. 16.
    Tombaugh TN, Kozak J, Rees L (1999) Normative data stratified by age and education for two measures of verbal fluency. Arch Clin Neuropsychol 14(2):167–177PubMedGoogle Scholar
  17. 17.
    Tombaugh TN, Rees L, McIntyre N (1998) Normative data for the trail making test. In: Spreen O, Strauss E (eds) A compendium of neuropsychological tests: administration. Oxford University Press, New YorkGoogle Scholar
  18. 18.
    Wechsler D (1997) Wechsler adult intelligence scale, 3rd revision (WAIS-III). Psychological Corporation, San AntonioGoogle Scholar
  19. 19.
    Kolb B, Whishaw IQ (1995) Fundamentals of human neuropsychology. Freeman Press, New YorkGoogle Scholar
  20. 20.
    Spreen O, Strauss E (1998) A compendium of neuropsychological tests: administration, norms and commentary, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  21. 21.
    Buschke H, Fuld P (1974) Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology 24:1019–1025PubMedGoogle Scholar
  22. 22.
    Sivan A (1992) Benton visual retention test. Psychological Corporation, New YorkGoogle Scholar
  23. 23.
    Beck AT, Beamesderfer A (1974) Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatr 7:151–169Google Scholar
  24. 24.
    Beck AT, Steer RA, Garbin MG (1988) Psychometric properties of the beck depression inventory: twenty-five years of evaluation. Clin Psychol Rev 8(1):77–100CrossRefGoogle Scholar
  25. 25.
    Zung WW (1973) The differentiation of anxiety and depressive disorders: a psychopharmacological approach. Psychosomatics 14(6):362–366PubMedGoogle Scholar
  26. 26.
    Bystritsky A, Linn LS, Ware JE (1990) Development of a multidimensional scale of anxiety. J Anxiety Disord 4(2):99–115CrossRefGoogle Scholar
  27. 27.
    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):2292–2299CrossRefPubMedGoogle Scholar
  28. 28.
    Zehnder AE, Blasi S, Berres M, Spiegel R, Monsch AU (2007) Lack of practice effects on neuropsychological tests as early cognitive markers of Alzheimer Disease? Am J Alzheimers Dis Other Demen 22:416–426CrossRefPubMedGoogle Scholar
  29. 29.
    Vardy J, Wefel JS, Ahles T, Tannock IF, Schagen SB (2008) Cancer and cancer-therapy related cognitive dysfunction: an international perspective from the Venice cognitive workshop. Ann Oncol 19(4):623–629CrossRefPubMedGoogle Scholar
  30. 30.
    Eberhardt B, Dilger S, Musial F, Wedding U, Weiss ET, Wolfgang HR, Miltner (2006) Short-term monitoring of cognitive functions before and during the first course of treatment. J Cancer Res Clin Oncol 132(4):234–240CrossRefPubMedGoogle Scholar
  31. 31.
    Meyers CA (2008) How chemotherapy damages the central nervous system. J Biol 7(4):11CrossRefPubMedGoogle Scholar
  32. 32.
    Stewart A, Collins B, Mackenzie J, Tomiak E, Verma S, Bielajew C (2008) The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology 17(2):122–130CrossRefPubMedGoogle Scholar
  33. 33.
    Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA (2004) Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol 26(7):955–969CrossRefPubMedGoogle Scholar
  34. 34.
    Wickham R (2007) Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clin J Oncol Nurs 11(3):361–376CrossRefPubMedGoogle Scholar
  35. 35.
    Jung BF, Ahrendt GM, Oaklander AL, Dworkin RH (2003) Neuropathic pain following breast cancer surgery: proposed classification and research update. Pain 104(1–2):1–13CrossRefPubMedGoogle Scholar
  36. 36.
    Jung BF, Herrmann D, Griggs J, Oaklander AL, Dworkin RH (2005) Neuropathic pain associated with non-surgical treatment of breast cancer. Pain 118(1–2):10–14CrossRefPubMedGoogle Scholar
  37. 37.
    Ratner DP, Adams KM, Levin NW, Rourke BP (1983) Effects of hemodialysis on the cognitive and sensory-motor functioning of the adult chronic hemodialysis patient. J Behav Med 6(3):291–311CrossRefPubMedGoogle Scholar
  38. 38.
    Llorente AM, Miller EN, D’Elia LF, Selnes OA, Wesch J, Becker JT, Satz P (1998) Slowed information processing in HIV-1 disease. The Multicenter AIDS Cohort Study (MACS). J Clin Exp Neuropsychol 20(1):60–72CrossRefPubMedGoogle Scholar
  39. 39.
    Vainionpaa L (1993) Clinical neurological findings of children with acute lymphoblastic leukaemia at diagnosis and during treatment. Eur J Pediatr 152(2):115–119CrossRefPubMedGoogle Scholar
  40. 40.
    Reinders-Messelink HA, Schoemaker MM, Hofte M, Goeken LN, Kingma A, van den Briel MM, Kamps WA (1996) Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia. Med Pediatr Oncol 27(6):551–555CrossRefPubMedGoogle Scholar
  41. 41.
    Copeland DR, Dowell RE Jr, Fletcher JM, Sullivan MP, Jaffe N, Cangir A, Frankel LS, Judd BW (1988) Neuropsychological test performance of pediatric cancer patients at diagnosis and one year later. J Pediatr Psychol 13(2):183–196CrossRefPubMedGoogle Scholar
  42. 42.
    Lehtinen S (2003) Neurotoxicity in children after treatment for acute lymphoblastic leukaemia and methotrexate neurotoxicity in a controlled animal model. Oulu University Press, Oulu, FinlandGoogle Scholar
  43. 43.
    Lezak MD (1995) Neuropsychological assessment, 3rd edn. Oxford University Press, New YorkGoogle Scholar
  44. 44.
    Hermelink K, Untch M, Lux M, Kreienberg R, Beck T, Bauerfeind I, Münzel K (2007) Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer 109(9):1905–1913CrossRefPubMedGoogle Scholar
  45. 45.
    Shilling V, Jenkins V (2007) Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer. Eur J Oncol Nurs 11(1):6–15CrossRefPubMedGoogle Scholar
  46. 46.
    Klepstad P, Hilton P, Moen J, Fougner B, Borchgrevink P, Kaasa S (2002) Self reports are not related to objective assessments of cognitive function and sedation in patients with cancer pain admitted to a palliative care unit. Palliat Med 16:513–519CrossRefPubMedGoogle Scholar
  47. 47.
    Saykin AJ, Janssen RS, Sprehn GC, Kaplan JE, Spira TJ, O’Connor B (1991) Longitudinal evaluation of neuropsychological function in homosexual men with HIV infection: 18-month follow-up. J Neuropsychiatry Clin Neurosci 3(3):286–298PubMedGoogle Scholar
  48. 48.
    Deutsch G, Saykin AJ, Sperling MR (1996) Metamemory in temporal lobe epilepsy. Assessment 3(3):255–263CrossRefGoogle Scholar
  49. 49.
    McAllister TW, Flashman LA, Sparling MB, Saykin AJ, Ferguson R, Yanofsky N (1999) Relationship of psychopathology to post-concussive symptoms one month after mild traumatic brain injury (MTBI). J Neuropsychiatry Clin Neurosci 11(1):150–151Google Scholar
  50. 50.
    Jansen CE, Miaskowski CA, Dodd MJ, Dowling GA (2007) A meta-analysis of the sensitivity of various neuropsychological tests used to detect chemotherapy-induced cognitive impairment in patients with breast cancer. Oncol Nurs Forum 34(5):997–1005CrossRefPubMedGoogle Scholar
  51. 51.
    Campbell D, Stanley J (1963) Experimental and quasi-experimental designs for research. Houghton Mifflin, BostonGoogle Scholar
  52. 52.
    Vardy J, Rourke S, Tannock IF (2007) Evaluation of cognitive function associated with chemotherapy: a review of published studies and recommendations for future research. J Clin Oncol 25:2455–2463CrossRefPubMedGoogle Scholar
  53. 53.
    Temkin NR, Heaton RK, Grant I, Dikmen SS (1999) Detecting significant change in neuropsychological test performance: a comparison of four models. J Int Neuropsychol Soc 5:357–369CrossRefPubMedGoogle Scholar
  54. 54.
    Heaton RK, Temkin N, Dikmen S, Avitable N, Taylor MJ, Marcotte TD, Grant I (2001) Detecting change: a comparison of three neuropsychological methods, using normal and clinical samples. Arch Clin Neuropsychol 16(1):75–91PubMedGoogle Scholar
  55. 55.
    Erlanger D, Feldman D, Kutner K, Kaushik T, Kroger H, Festa J, Barth J, Freeman J, Broshek D (2003) Development and validation of a web-based neuropsychological test protocol for sports-related return-to-play decision-making. Arch Clin Neuropsychol 18(3):293–316PubMedGoogle Scholar
  56. 56.
    Ouimet LA, Stewart A, Collins B, Schindler D, Bielajew C (2008) Measuring neuropsychological change following breast cancer treatment: an analysis of statistical models. J Clin Exp Neuropsychol 31(1):73–89Google Scholar
  57. 57.
    Jenkins VA, Ambroisine LM, Atkins L, Cuzick J, Howell A, Fallowfield L (2008) Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet Oncol 9:953–961CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Felice A. Tager
    • 1
    • 4
  • Paula S. McKinley
    • 1
    • 4
  • Freya R. Schnabel
    • 6
  • Mahmoud El-Tamer
    • 3
  • Ying Keun K. Cheung
    • 5
  • Yixin Fang
    • 7
  • Claire R. Golden
    • 1
  • Margery E. Frosch
    • 1
  • Ulya Habif
    • 1
  • Margaret M. Mulligan
    • 1
  • Ivy S. Chen
    • 1
  • Dawn L. Hershman
    • 2
    • 4
    • 5
  1. 1.Behavioral Medicine Program, Department of Psychiatry, College of Physicians and SurgeonsColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Medicine, College of Physicians and SurgeonsColumbia University Medical CenterNew YorkUSA
  3. 3.Department of Surgical Oncology, College of Physicians and SurgeonsColumbia University Medical CenterNew YorkUSA
  4. 4.Herbert Irving Comprehensive Cancer Center, College of Physicians and SurgeonsColumbia University Medical CenterNew YorkUSA
  5. 5.Departments of Epidemiology and Biostatistics, Mailman School of Public HealthColumbia University Medical CenterNew YorkUSA
  6. 6.Department of Surgical OncologyNew York University Medical CenterNew YorkUSA
  7. 7.Department of Mathematics and StatisticsGeorgia State UniversityAtlantaGAUSA

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