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

  • Epidemiology
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Abstract

Purpose

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

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

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.

Funding

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.

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Authors and Affiliations

  1. Department of Public Health Sciences, College of Medicine, The Pennsylvania State University, 500 University Drive, Hershey, PA, 17033, USA

    Shirley M. Bluethmann

  2. American Cancer Society, Inc., 1875 Connecticut Ave NW, Washington, DC, 20009, USA

    Catherine M. Alfano

  3. Department of Oncology, Georgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer Center, 3300 Whitehaven Street NW, suite 4100, Washington, DC, 20007, USA

    Jonathan D. Clapp & Jeanne S. Mandelblatt

  4. Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer Center, 3300 Whitehaven Street NW, suite 4100, Washington, DC, 20007, USA

    George Luta

  5. School of Aging Studies, University of South Florida, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Brent J. Small

  6. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 Duarte Rd, Duarte, CA, 91010, USA

    Arti Hurria

  7. Department of Medicine and Center for the Study of Aging and Human Development, Duke University, DUMC, Room 3502 Busse Building, Blue Zone, Duke South, Box 3003, Durham, NC, 27710, USA

    Harvey J. Cohen

  8. Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Steven Sugarman

  9. Department of Medicine, UNC-Chapel Hill School of Medicine, University of North Carolina, 321 South Columbia Street, Chapel Hill, NC, 27514, USA

    Hyman B. Muss

  10. Department of Medicine, Georgetown University Medical Center and Georgetown-Lombardi Comprehensive Cancer Center, 3300 Whitehaven Street NW, suite 4100, Washington, DC, 20007, USA

    Claudine Isaacs & Jeanne S. Mandelblatt

Authors
  1. Shirley M. Bluethmann
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  2. Catherine M. Alfano
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  4. George Luta
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  6. Arti Hurria
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  7. Harvey J. Cohen
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  10. Claudine Isaacs
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  11. Jeanne S. Mandelblatt
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Corresponding author

Correspondence to Shirley M. Bluethmann.

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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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Bluethmann, S.M., Alfano, C.M., Clapp, J.D. et al. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance). Breast Cancer Res Treat 165, 677–686 (2017). https://doi.org/10.1007/s10549-017-4353-y

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  • DOI: https://doi.org/10.1007/s10549-017-4353-y

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