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Breast Cancer Research and Treatment

, Volume 126, Issue 1, pp 221–226 | Cite as

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

  • Kelly-Anne Phillips
  • Julie Aldridge
  • Karin Ribi
  • Zhuoxin Sun
  • Alastair Thompson
  • Vernon Harvey
  • Beat Thürlimann
  • Fatima Cardoso
  • Olivia Pagani
  • Alan S. Coates
  • Aron Goldhirsch
  • Karen N. Price
  • Richard D. Gelber
  • Jürg BernhardEmail author
Brief Report

Abstract

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment.

Keywords

Cognitive function Breast cancer Aromatase inhibitor Tamoxifen Letrozole Quality of life 

Notes

Acknowledgment

We thank the patients who participated in this trial, collaborators, and funding sources. Acknowledgment for respective individuals involved in the various groups is given in the Appendix. This work was supported by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute at the National Institutes of Health (Grant number CA-75362); Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK);The Cancer Council Victoria, Dr. John Colebatch Clinical Research Fellowship (to K.A.P).

Conflict of interest

Financial disclosures: The substudy was funded by Novartis. Novartis contracted with the International Breast Cancer Study Group (IBCSG) for provision of services related to the conduct and management of the trial. Dr. Thürlimann owns stock in Novartis; Dr. Cardoso has received consulting and/or lecture fees from Novartis, Dr. Thompson and Dr. Goldhirsch have received honoraria from Novartis. The remaining authors have no conflicts to report.

References

  1. 1.
    McCarty KS Jr, Silva JS, Cox EB et al (1983) Relationship of age and menopausal status to estrogen receptor content in primary carcinoma of the breast. Ann Surg 197:123–127CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Schilder CM, Seynaeve C, Beex WB et al (2010) 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. J Clin Oncol 28:1294–1300CrossRefPubMedGoogle Scholar
  3. 3.
    Collins B, Mackenzie J, Stewart A et al (2009) Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study. Psychooncology 18:811–821CrossRefPubMedGoogle Scholar
  4. 4.
    Bender CM, Sereika SM, Berga SL et al (2006) Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncology 15:422–430CrossRefPubMedGoogle Scholar
  5. 5.
    Jenkins V, Shilling V, Fallowfield L et al (2004) Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? a pilot study. Psychooncology 13:61–66CrossRefPubMedGoogle Scholar
  6. 6.
    Phillips KA, Ribi K, Sun Z et al (2010) Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomised trial. Breast 19:388–395CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Jenkins V, Ambroisine LM, Atkins L et al (2008) Effects of anastrozole on cognitive performance in postmenopausal women: a randomized, double-blind chemoprevention trial (IBIS II). Lancet Oncol 9:953–961CrossRefPubMedGoogle Scholar
  8. 8.
    BIG 1-98 Collaborative Group (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757CrossRefGoogle Scholar
  9. 9.
    BIG 1-98 Collaborative Group (2009) Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 361:766–776CrossRefGoogle Scholar
  10. 10.
    Vardy J, Wong K, Yi QL et al (2006) Assessing cognitive function in cancer patients. Support Care Cancer 14:1111–1118CrossRefPubMedGoogle Scholar
  11. 11.
    Falleti MG, Maruff P, Collie A et al (2003) Qualitative similarities in cognitive impairment associated with 24 h of sustained wakefulness and a blood alcohol concentration of 0.05%. J Sleep Res 12:265–274CrossRefPubMedGoogle Scholar
  12. 12.
    Snyder PJ, Werth J, Giordani B et al (2005) A method for determining the magnitude of change across difference cognitive functions in clinical trials: the effects of acute administration of two different doses of alprazolam. Hum Psychopharmacol 20:263–273CrossRefPubMedGoogle Scholar
  13. 13.
    Collie A, Darby D, Maruff P (2001) Computerized cognitive assessment of athletes with sports related head injury. Br J Sports Med 35:279–302CrossRefGoogle Scholar
  14. 14.
    Maruff P, Thomas E, Cysique L et al (2009) Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch Clin Neuropsychol 24:165–178CrossRefPubMedGoogle Scholar
  15. 15.
    Silber BY, Croft RJ, Papafotiou K, Stough C (2006) The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance. Psychopharmacology 187:154–169CrossRefPubMedGoogle Scholar
  16. 16.
    Fillmore MT, Kelly TH, Martin CA (2005) Effects of d-amphetamine in human models of information processing and inhibitory control. Drug Alcohol Depend 77:151–159CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Buchanan RW, Keefe RS, Umbricht D et al The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later? Schizophr Bull (in press)Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Kelly-Anne Phillips
    • 1
  • Julie Aldridge
    • 2
  • Karin Ribi
    • 3
  • Zhuoxin Sun
    • 2
  • Alastair Thompson
    • 4
  • Vernon Harvey
    • 5
    • 6
  • Beat Thürlimann
    • 7
    • 8
  • Fatima Cardoso
    • 9
  • Olivia Pagani
    • 8
    • 10
  • Alan S. Coates
    • 11
    • 12
  • Aron Goldhirsch
    • 13
    • 14
  • Karen N. Price
    • 15
  • Richard D. Gelber
    • 16
  • Jürg Bernhard
    • 17
    • 18
    Email author
  1. 1.Peter MacCallum Cancer CentreThe University of MelbourneMelbourneAustralia
  2. 2.IBCSG Statistical CenterDana-Farber Cancer InstituteBostonUSA
  3. 3.IBCSG Coordinating CenterBernSwitzerland
  4. 4.Ninewells HospitalUniversity of DundeeDundeeScotland, UK
  5. 5.Auckland City HospitalAucklandNew Zealand
  6. 6.Australian New Zealand Breast Cancer Trials GroupNewcastleAustralia
  7. 7.Breast CenterKantonsspitalSt. GallenSwitzerland
  8. 8.Swiss Group for Clinical Cancer Research (SAKK)BernSwitzerland
  9. 9.Department of Medical OncologyJules Bordet InstituteBrusselsBelgium
  10. 10.Oncology Institute of Southern SwitzerlandOspedale ItalianoLuganoSwitzerland
  11. 11.International Breast Cancer Study GroupBernSwitzerland
  12. 12.University of SydneySydneyAustralia
  13. 13.Department of MedicineEuropean Institute of OncologyMilanItaly
  14. 14.Oncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  15. 15.IBCSG Statistical Center, Frontier Science and Technology Research FoundationDana-Farber Cancer InstituteBostonUSA
  16. 16.IBCSG Statistical Center, Frontier Science and Technology Research FoundationDana-Farber Cancer InstituteBostonUSA
  17. 17.IBCSG Coordinating CenterBernSwitzerland
  18. 18.Department of Medical OncologyInselspital, Bern University HospitalBernSwitzerland

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