Skip to main content

Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls

Journal of Cancer Survivorship volume 2, pages 275–282 (2008)Cite this article

Abstract

Introduction

The selective estrogen receptor modulator, Tamoxifen (TAM), is one of the most frequently prescribed drugs for the treatment of breast cancer; however, its effects on the cognition of users have not been adequately studied. Although TAM is an effective anti-estrogen that blocks tumour growth in the breast, it could also influence the activity of other target estrogen sites, including the brain. The exact nature of this interaction is unknown.

Methods

A cross-sectional design was used to compare cognitive task performance of two treatment groups: 1) women using TAM for the treatment of early breast cancer (n = 23); and 2) age-matched, healthy women not using TAM (n = 23). All participants were pre-menopausal, and recipients of chemotherapy were excluded from the study.

Results

It was found that TAM users scored significantly worse than controls on tasks of immediate and delayed visual memory, verbal fluency, immediate verbal memory, visuo-spatial ability, and processing speed.

Discussions/Conclusions

Although limited by the lack of baseline data and pre-morbid intelligence measures, the results of this exploratory study suggest that at least in pre-menopausal women, TAM may exert a widespread negative influence on cognitive abilities.

Implications for Cancer Survivors

Larger, randomized, prospective trials are required to confirm these results; however, TAM use in pre-menopausal breast cancer may be associated with cognitive difficulties. Knowledge and understanding of these complications will be important for professionals in communicating both the benefits and risks of TAM use in breast cancer survivors.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Jaiyesimi IA, Buzdar AU, Decker DA, Hortobagyi GN. Use of Tamoxifen for breast cancer: Twenty-eight years later. J Clin Oncol 1995;13:513–29.

    PubMed  CAS  Google Scholar 

  2. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998;339:1609–18. doi:10.1056/NEJM199811263392207.

    PubMed  Article  CAS  Google Scholar 

  3. Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, 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. doi:10.1200/JCO.20.2.485.

    PubMed  Article  CAS  Google Scholar 

  4. Castellon SA, Ganz PA, Bower JE, Peterson L, Abraham L, Greendale GA. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol 2004;26:955–69. doi:10.1080/13803390490510905.

    PubMed  Article  Google Scholar 

  5. Bender CM, Sereika SM, Berga SL, Vogel VG, Brufsky AM, Paraska KK, et al. Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncol 2006;15:422–30. doi:10.1002/pon.964.

    Article  Google Scholar 

  6. van Dam FSAM, Schagen SB, Muller MJ, Boogerd W, van der Wall E, Droogleever Fortuyn ME, 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. doi:10.1093/jnci/90.3.210.

    PubMed  Article  Google Scholar 

  7. McEwen B, Alves SE. Estrogen action in the CNS. Endocr Rev 1999;20:279–307. doi:10.1210/er.20.3.279.

    PubMed  Article  CAS  Google Scholar 

  8. Woolley C. Effects of estrogen in the CNS. Curr Opin Neurobiol 1999;9:349–54. doi:10.1016/S0959-4388(99)80051-8.

    PubMed  Article  CAS  Google Scholar 

  9. Wooley C, McEwen B. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 1992;12:2549–54.

    Google Scholar 

  10. Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, VanHorn JD, Esposito G, et al. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proc Natl Acad Sci USA 1997;94:8836–41. doi:10.1073/pnas.94.16.8836.

    PubMed  Article  CAS  Google Scholar 

  11. Birge SJ, McEwen BS, Wise PM. Effects of estrogen deficiency on brain function. Postgrad Med. 2001, S11–S15, (March).

  12. Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ. Estrogen- and tamoxifen-associated effects on brain structure and function. Neuroimage 2004;21:364–71. doi:10.1016/j.neuroimage.2003.08.037.

    PubMed  Article  Google Scholar 

  13. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S. Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Mol Pharmacol 1998;54:105–12.

    PubMed  CAS  Google Scholar 

  14. Hampson E. Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn 1990;14:26–43. doi:10.1016/0278-2626(90)90058-V.

    PubMed  Article  CAS  Google Scholar 

  15. Kimura D. Estrogen replacement therapy may protect against intellectual decline in post-menopausal women. Horm Behav 1995;29:312–21. doi:10.1006/hbeh.1995.1022.

    PubMed  Article  CAS  Google Scholar 

  16. Phillips SM, Sherwin B. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology 1992;17:497–506. doi:10.1016/0306-4530(92)90008-U.

    PubMed  Article  CAS  Google Scholar 

  17. Sherwin B, Tulandi T. “Add-back” estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with Leiomyomata Uteri. J Clin Endocrin Metab 1996;81:2545–49. doi:10.1210/jc.81.7.2545.

    Article  CAS  Google Scholar 

  18. Duff SJ, Hampson E. A beneficial effect of estrogen on working memory in post-menopausal women taking hormone replacement therapy. Horm Behav 2000;38:262–76. doi:10.1006/hbeh.2000.1625.

    PubMed  Article  CAS  Google Scholar 

  19. Keenan PA, Ezzat WH, Ginsburg K, Moore GJ. Prefrontal cortex as the site of estrogen’s effect on cognition. Psychoneuroendocrinology 2001;26:577–90. doi:10.1016/S0306-4530(01)00013-0.

    PubMed  Article  CAS  Google Scholar 

  20. Grigorova M, Sherwin BB, Tulandi T. Effects of treatment with leuprolide acetate depot on working memory and executive functions in young premenopausal women. Psychoneuroendocrinology 2006;31:935–47. doi:10.1016/j.psyneuen.2006.05.004.

    PubMed  Article  CAS  Google Scholar 

  21. Silverman I, Phillips K. Effects of estrogen changes during the menstrual cycle on spatial performance. Ethol Sociobiol 1993;14:257–70. doi:10.1016/0162-3095(93)90021-9.

    Article  Google Scholar 

  22. Brezden CB, Phillips K, Abdolell M, Bunston T, Tannock IF. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2000;18:2695–701.

    PubMed  CAS  Google Scholar 

  23. Paraska KK, Bender CM. Cognitive dysfunction following adjuvant chemotherapy for breast cancer: two case studies. Oncol Nurs Forum 2003;30:473–78. doi:10.1188/03.ONF.473-478.

    PubMed  Article  Google Scholar 

  24. Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with, breast carcinoma. Cancer 2004;100:2292–9. doi:10.1002/cncr.20272.

    PubMed  Article  CAS  Google Scholar 

  25. Paganini-Hill A, Clark LJ. Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 2000;64:165–76. doi:10.1023/A:1006426132338.

    PubMed  Article  CAS  Google Scholar 

  26. Shilling V, Jenkins V, Fallowfield L, Howell T. The effects of hormone therapy on cognition in breast cancer. J Steroid Biochem 2003;86:405–12. doi:10.1016/j.jsbmb.2003.07.001.

    Article  CAS  Google Scholar 

  27. McNair DM, Lorr M, Droppleman LF. Profile of mood states. San Diego, California: EdITS/Educational and Industrial Testing Service; 1992.

    Google Scholar 

  28. Meyers J, Meyers K. The Meyers scoring system for the Rey complex figure and recognition trial: professional manual. Odessa, FA: Psychological Assessment Resources; 1995.

    Google Scholar 

  29. Wechsler D. Wechsler memory scale. 3rd ed. San Antonio, TX: The Psychological Corporation; 1997.

    Google Scholar 

  30. Vandenberg SG, Kuse AR. Mental rotations: a group test of three-dimensional spatial visualization. Percept Mot Skills 1978;47:599–604.

    PubMed  CAS  Google Scholar 

  31. Wechsler D. Wechsler adult intelligence scale-III. New York, NY: The Psychological Corporation; 1991.

    Google Scholar 

  32. Spreen O, Strauss E. A compendium of neuropsychological tests. 2nd ed. New York, NY: Oxford University; 1998. p. 263–7. 447–464.

    Google Scholar 

  33. Kimura D. Sex and cognition. Cambridge, MA: MIT; 1999.

    Google Scholar 

  34. Cimprich B, Ronis DL. Attention and symptom distress in women with and without breast cancer. Nurs Res 2001;50:86–94. doi:10.1097/00006199-200103000-00004.

    PubMed  Article  CAS  Google Scholar 

  35. Hurria A, Rosen C, Hudis C, Zuckerman E, Panageas KS, Lachs MS. Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: A pilot prospective longitudinal study. J Am Geriatr Soc 2006;54:925–31. doi:10.1111/j.1532-5415.2006.00732.x.

    PubMed  Article  Google Scholar 

  36. Wefel JS, Lenzi R, Theriault R, Davis RN, Meyers CA. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast cancer. Cancer 2004;100:2292-9. doi:10.1002/cncr.20272.

    PubMed  Article  Google Scholar 

  37. Yeudall LT, Fromm D, Reddon JR, Stefanyk WO. Normative data stratified by age and sex for 12 neuropsychological tests. J Clin Psychol 1986;42:918–46. doi:10.1002/1097-4679(198611)42:6<918::AID-JCLP2270420617>3.0.CO;2-Y.

    Article  Google Scholar 

  38. Lafayette Instrument Company. Instructions and normative data for model 32020 Purdue Pegboard. Lafayette, IN: Lafayette Instrument Company; 1985.

    Google Scholar 

  39. Eals M, Silverman I. The hunter-gatherer theory of spatial sex differences: proximate factors mediating the female advantage in recall of object arrays. Ethol Sociobiol 1994;15:95–105. doi:10.1016/0162-3095(94)90020-5.

    Article  Google Scholar 

  40. Silverman I, Eals M. Sex differences in spatial abilities: evolutionary theory and data. In: Barkow J, Cosmides L, Tooby J, editors. The adapted mind: evolutionary psychology and the generation of culture. New York, NY: Oxford University Press; 1992. p. 487–503.

    Google Scholar 

  41. Kaplan EF, Goodglass H, Weintraub S. The Boston naming test. 2nd ed. Austin, TX: Pro-Ed; 2001.

    Google Scholar 

Download references

Acknowledgements

This research was funded by a grant from the Alberta Cancer Board through the Tom Baker Cancer Centre Clinical Research Unit. Dr. Carlson holds the Enbridge Endowed Research Chair in Psychosocial Oncology and an Alberta Heritage Foundation for Medical Research Health Scholar Award.

Author information

Affiliations

  1. Division of Applied Psychology, University of Calgary, Calgary, AB, Canada

    Jaime L. Palmer

  2. Tom Baker Cancer Centre, Alberta Cancer Board, 1331-29 Street NW, Calgary, AB, Canada, T2N 4N2

    Theresa Trotter

  3. Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, Canada, T6G 1Z2

    Anil A. Joy

  4. Division of Psychosocial Oncology, Department of Oncology, University of Calgary, Calgary, AB, Canada

    Linda E. Carlson

  5. Alberta Cancer Board-Holy Cross Site, 2202 - 2 Street SW, Calgary, AB, Canada, T2S 3C1

    Linda E. Carlson

Authors
  1. Jaime L. Palmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theresa Trotter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anil A. Joy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Linda E. Carlson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Linda E. Carlson.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Palmer, J.L., Trotter, T., Joy, A.A. et al. Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls. J Cancer Surviv 2, 275–282 (2008). https://doi.org/10.1007/s11764-008-0070-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11764-008-0070-1

Keywords

  • Estrogens
  • Estrogen receptor modulators
  • Breast neoplasms
  • Neuro-behavioural manifestations
  • Pre-menopause
  • Tamoxifen