Breast Cancer Research and Treatment

, Volume 165, Issue 3, pp 677–686 | Cite as

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance)

  • Shirley M. BluethmannEmail author
  • Catherine M. Alfano
  • Jonathan D. Clapp
  • George Luta
  • Brent J. Small
  • Arti Hurria
  • Harvey J. Cohen
  • Steven Sugarman
  • Hyman B. Muss
  • Claudine Isaacs
  • Jeanne S. Mandelblatt



To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ (“older”).


Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0–100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1–3 years); and late discontinuation (>3–5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates.


Survivors were 65–91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09–1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods.


Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1–3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.


Survivorship Adjuvant therapy Aging Cognition Cognitive function 



Earlier versions of this research were presented by Dr. Bluethmann at the International Association of Gerontology and Geriatrics World Congress, July 23–27, 2017, San Francisco, CA.


This research was conducted under Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) Protocol #369901. The research infrastructure was supported by UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA031946, U10C0A33601, U10CA032291, U10CA047559, U10CA047577, U10CA077597, U10CA077651, U10CA180791, U10CA180857, U10CA180867, U10CA180838, and U10CA84131 to the Alliance. The research was also supported, in part, by NCI Grants R35CA197289, R01CA129769, R01CA124924, and K05CA96940 to JSM; and the Biostatistics and Bioinformatics Shared Resources at Georgetown-Lombardi Comprehensive Cancer Center funded by the National Cancer Institute at the National Institutes of Health under grant P30CA051008. Dr. Bluethmann was funded through the Cancer Prevention Fellowship at the National Cancer Institute at the time this report was prepared. Earlier portions of the research were also funded in part by a grant to support patient accrual from Amgen Pharmaceuticals to the CALGB Foundation. The content of this manuscript is solely the responsibility of the authors and does not represent the official views of the National Cancer Institute at the National Institutes of Health or the Alliance for Clinical Trials in Oncology.

Compliance with ethical standards

Conflict of interest

Dr. Isaacs received remuneration and funding from Astra Zeneca, Pfizer, and Novartis. She is also a consultant/advisor for Astra Zeneca, Novartis, and Nanostring Technologies. Dr. Hurria is a consultant for Pierian Bioscience and Boehringer Ingelheim. She has also received funded from Celgene, Novartis, and GlaxoSmithKline. All other authors declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. The protocol met Health Insurance Portability and Accountability Act standards and was approved by CALGB, the National Cancer Institute, and the institutional review boards at all sites. Each participant signed an IRB-approved, protocol-specific consent form in accordance with federal and institutional guidelines.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Shirley M. Bluethmann
    • 1
    Email author
  • Catherine M. Alfano
    • 2
  • Jonathan D. Clapp
    • 3
  • George Luta
    • 4
  • Brent J. Small
    • 5
  • Arti Hurria
    • 6
  • Harvey J. Cohen
    • 7
  • Steven Sugarman
    • 8
  • Hyman B. Muss
    • 9
  • Claudine Isaacs
    • 10
  • Jeanne S. Mandelblatt
    • 3
    • 10
  1. 1.Department of Public Health Sciences, College of MedicineThe Pennsylvania State UniversityHersheyUSA
  2. 2.American Cancer Society, Inc.WashingtonUSA
  3. 3.Department of OncologyGeorgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer CenterWashingtonUSA
  4. 4.Department of Biostatistics, Bioinformatics and BiomathematicsGeorgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer CenterWashingtonUSA
  5. 5.School of Aging StudiesUniversity of South Florida, Moffitt Cancer CenterTampaUSA
  6. 6.Department of Medical Oncology and Therapeutics ResearchCity of Hope Comprehensive Cancer CenterDuarteUSA
  7. 7.Department of Medicine and Center for the Study of Aging and Human DevelopmentDuke UniversityDurhamUSA
  8. 8.Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  9. 9.Department of Medicine, UNC-Chapel Hill School of MedicineUniversity of North CarolinaChapel HillUSA
  10. 10.Department of MedicineGeorgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer CenterWashingtonUSA

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