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Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study

  • Epidemiology
  • Published:
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Abstract

Purpose

Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients.

Methods

Women diagnosed with non-metastatic breast cancer (n = 705) ages 60–98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score).

Results

HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM.

Conclusions

Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.

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Data availability

The data collected for the Thinking and Living with Cancer (TLC) Study used in this publication were supported by funding from the National Institutes of Health. The data are available for sharing under NIH-compliant TLC Study agreements. Please contact the corresponding author for requests.

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Acknowledgements

The work of Paul Jacobsen was done while he was at Moffitt Cancer Center. We would like to thank the participants in the TLC study for their sharing of their time and experiences; without their generosity this study would not have been possible. We are also indebted to Sherri Stahl, Naomi Greenwood, Margery London, and Sue Winarsky who serve as patient advocates from the Georgetown Breast Cancer Advocates for their insights and suggestions on study design and methods to recruit and retain participants. We thank the TLC study staff who contributed by ascertaining, enrolling and interviewing participants.

Funding

This research was supported by the National Cancer Institute at the National Institutes of Health Grants R01CA129769 and R35CA197289 to JM. This study was also supported in part by the National Cancer Institute at the National Institutes of Health Grant P30CA51008 to Georgetown-Lombardi Comprehensive Cancer Center for support of the Biostatistics and Bioinformatics Resource and the Non-Therapeutic Shared Resource. The work of AJS and BCM was supported in part by the National Institute on Aging, National Library of Medicine, and National Cancer Institute at the National Institutes of Health Grants P30AG10133, R01AG19771, R01LM01136, and R01CA244673. TAA and JCR were supported in part by National Cancer Institute at the National Institutes of Health Grants R01 CA218496, R01CA172119, R03CA249548, and P30CA008748. The work of JC was supported in part by the American Cancer Society Research Scholars Grant 128660-RSG-15–187-01-PCSM and the National Cancer Institute at the National Institutes of Health grant R01CA237535. HJC was supported in part by the National Institute of Aging at the National Institutes of Health Grant P30AG028716 for the Duke Pepper Center. SKP was supported in part by the American Cancer Society Research Scholars Grant RSG-17–023-01-CPPB.

Author information

Author notes

  1. Mandelblatt and Ahles have contributed equally as senior authors.

Authors and Affiliations

  1. Neurocognitive Research Lab, Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue, 7th Floor, New York, NY, USA

    James C. Root & Tim A. Ahles

  2. Departments of Psychiatry and Anesthesiology, Weill Medical College of Cornell University, New York, NY, USA

    James C. Root

  3. Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Xingtao Zhou, Jaeil Ahn & Wanting Zhai

  4. School of Aging Studies, University of South Florida, and Senior Member, Health Outcome and Behavior Program and Biostatistics Resource Core, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL, USA

    Brent J. Small

  5. Department of Oncology, Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Traci Bethea & Jeanne S. Mandelblatt

  6. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Jane and Terry Semel Institute for Neuroscience and Human BehaviorJonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA

    Judith E. Carroll, Kelly Rentscher & Kathleen Van Dyk

  7. Center for the Study of Aging and Human Development and Comprehensive Cancer Center, Duke University School of Medicine, Durham, NC, USA

    Harvey Jay Cohen

  8. MedStar Washington Hospital Center, MedStar Georgetown Lombardi Comprehensive Cancer Center, Washington, USA

    Asma Dilawari

  9. Department of Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    Martine Extermann & Heather Jim

  10. John Theurer Cancer Center, Hackensack, NJ, USA

    Deena Graham

  11. Departments of Oncology and Medicine, Breast Cancer Program, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Claudine Isaacs

  12. Healthcare Delivery Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA

    Paul B. Jacobsen

  13. Department of Health Outcomes and Behavior, Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL, USA

    Heather Jim

  14. Center for Neuroimaging, Department of Radiology and Imaging Sciences and the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    Brenna C. McDonald & Andrew J. Saykin

  15. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Zev M. Nakamura

  16. Departments of Population Sciences and Supportive Care Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Sunita K. Patel

Authors
  1. James C. Root
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  2. Xingtao Zhou
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  3. Jaeil Ahn
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  4. Brent J. Small
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  5. Wanting Zhai
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  6. Traci Bethea
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  7. Judith E. Carroll
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  8. Harvey Jay Cohen
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  9. Asma Dilawari
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  10. Martine Extermann
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  11. Deena Graham
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  12. Claudine Isaacs
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  13. Paul B. Jacobsen
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  14. Heather Jim
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  15. Brenna C. McDonald
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  18. Kelly Rentscher
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  19. Andrew J. Saykin
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  20. Kathleen Van Dyk
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  21. Jeanne S. Mandelblatt
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  22. Tim A. Ahles
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Contributions

JCR was responsible for investigation, supervision, and writing. XZ was responsible for formal analysis, data curation, and writing. JA was responsible for supervision, methodology, formal analysis, data curation, and writing. BJ Small was responsible for supervision, methodology, formal analysis, data curation, and writing. WZ was responsible for formal analysis, data curation, and writing. TB was responsible for conceptualization and writing. JC was responsible for conceptualization and writing. HJC was responsible for conceptualization and writing and editing. AD was responsible for conceptualization and writing. ME was responsible for conceptualization and writing. DG was responsible for investigation, resources, and writing. PBJ was responsible for investigation and writing. Heather Jim was responsible for investigation, resources, writing, project administration, and funding acquisition. CI was responsible for conceptualization and writing. BCM was responsible for investigation and writing. ZN was responsible for conceptualization and writing. SKP was responsible for investigation, resources, writing, and project administration. KR was responsible for conceptualization and writing. AJS was responsible for investigation, resources, writing, project administration, and funding acquisition. KvD was responsible for conceptualization and writing. JSM was responsible for conceptualization, investigation, resources, writing and editing, supervision, project administration, and funding acquisition. TA was responsible for conceptualization, investigation, resources, writing, project administration, and funding acquisition.

Corresponding author

Correspondence to James C. Root.

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Competing interest

Asma Dilawari has served on the Cardinal Health oncology summit advisor board, 2019. Claudine Isaacs has served as a consultant for Genentech, Seattle Genetics, PUMA, Novartis, AstraZeneca, Sanofi, and Pfizer, and received support for research (to institution) from Pfizer and Tesaro/GSK. Heather Jim has consulted for RedHill BioPharma, Janssen Scientific Affairs, and Merck, and has received grant funding from Kite Pharma. The other authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.

Ethical approval

This Institutional Review Board-approved study (ClinicalTrials.gov Identifier: NCT03451383) has been reported previously [2, 8] and was conducted at six US sites in Los Angeles, New York City, New Jersey, the DC metropolitan area, Indianapolis, and Tampa.

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The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.

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Root, J.C., Zhou, X., Ahn, J. et al. Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study. Breast Cancer Res Treat 194, 413–422 (2022). https://doi.org/10.1007/s10549-022-06623-2

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