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Long-term changes of cognitive impairment among older breast cancer survivors

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Abstract

Purpose

Cancer-related cognitive impairment is common during cancer treatment; however, it is unclear whether the impairment persists over time. Our study aimed to examine long-term cognitive impairment among older breast cancer survivors.

Methods

Participants included 2420 community-dwelling women aged 65 years or older at enrollment (1986–1988) (404 breast cancer cases and 1:5 matched cancer-free controls) from the Study of Osteoporotic Fractures. Participants were followed for 20 years with measured cognitive function repeated up to 6 times. Cognitive impairment was defined by the Modified Mini-Mental State Examination and Trail Making Test B. Generalized linear models were used to model risk of cognitive impairment in relation to breast cancer status and time from breast cancer diagnosis.

Results

Compared with controls, cognitive impairment in women with breast cancer significantly accelerated after cancer diagnosis. We also observed a more pronounced cognitive impairment after cancer diagnosis for women diagnosed with breast cancer at age ≥ 80 years or at advanced stage for both measures.

Conclusion

Our study with more than 20 years of follow-up data found that breast cancer survivors had accelerated cognitive impairment after cancer diagnosis, especially among women diagnosed at older age or at advanced stage, relative to women without cancer.

Implications for Cancer Survivors.

Breast cancer survivors may be encouraged to engage in both physical activity and cognitive training.

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Data availability

Data were available from the National Institute on Aging (NIA) AgingResearchBiobank (https://agingresearchbiobank.nia.nih.gov/) on reasonable request.

References

  1. ACS, Breast Cancer Facts & Figures 2019–2020 https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf. 2021, American Cancer Society (ACS).

  2. Kroenke CH, Rosner B, Chen WY, Kawachi I, Colditz GA, Holmes MD. Functional impact of breast cancer by age at diagnosis. J Clin Oncol. 2004;22(10):1849–56. https://doi.org/10.1200/Jco.2004.04.173.

    Article  PubMed  Google Scholar 

  3. Michael YL, Kawachi I, Berkman LF, Holmes MD, Colditz GA. The persistent impact of breast carcinoma on functional health status: prospective evidence from the Nurses’ Health Study. Cancer. 2000;89(11):2176–86. https://doi.org/10.1002/1097-0142(20001201)89:11%3c2176::aid-cncr5%3e3.0.co;2-6.

    Article  CAS  PubMed  Google Scholar 

  4. Karlsen RV, Frederiksen K, Larsen MB, von Heymann-Horan AB, Appel CW, Christensen J, et al. The impact of a breast cancer diagnosis on health-related quality of life. A prospective comparison among middle-aged to elderly women with and without breast cancer. Acta Oncol. 2016;55(6):720–7. https://doi.org/10.3109/0284186X.2015.1127415.

    Article  PubMed  Google Scholar 

  5. Michael YL, Wu C, Pan K, Seguin-Fowler RA, Garcia DO, Zaslavsky O, et al. Postmenopausal breast cancer and physical function change: a difference-in-differences analysis. J Am Geriatr Soc. 2020;68(5):1029–36. https://doi.org/10.1111/jgs.16323.

    Article  PubMed  Google Scholar 

  6. CDC. Cognitive impairement: a call for action, now! https://www.cdc.gov/aging/pdf/cognitive_impairment/cogimp_poilicy_final.pdf. 2011 [cited 2022 April 15].

  7. Orszaghova Z, Mego M, Chovanec M. Long-term cognitive dysfunction in cancer survivors. Front Mol Biosci. 2021;8:770413. https://doi.org/10.3389/fmolb.2021.770413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hodgson KD, Hutchinson AD, Wilson CJ, Nettelbeck T. A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. Cancer Treat Rev. 2013;39(3):297–304. https://doi.org/10.1016/j.ctrv.2012.11.001.

    Article  CAS  PubMed  Google Scholar 

  9. Jim HS, Phillips KM, Chait S, Faul LA, Popa MA, Lee YH, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. J Clin Oncol. 2012;30(29):3578–87. https://doi.org/10.1200/JCO.2011.39.5640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lange M, Joly F, Vardy J, Ahles T, Dubois M, Tron L, et al. Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Ann Oncol. 2019;30(12):1925–40. https://doi.org/10.1093/annonc/mdz410.

    Article  CAS  PubMed  Google Scholar 

  11. Lee PE, Tierney MC, Wu W, Pritchard KI, Rochon PA. Endocrine treatment-associated cognitive impairment in breast cancer survivors: evidence from published studies. Breast Cancer Res Treat. 2016;158(3):407–20. https://doi.org/10.1007/s10549-016-3906-9.

    Article  CAS  PubMed  Google Scholar 

  12. Shibayama O, Yoshiuchi K, Inagaki M, Matsuoka Y, Yoshikawa E, Sugawara Y, et al. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy. Cancer Med. 2014;3(3):702–9. https://doi.org/10.1002/cam4.174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dijkshoorn ABC, van Stralen HE, Sloots M, Schagen SB, Visser-Meily JMA, Schepers VPM. Prevalence of cognitive impairment and change in patients with breast cancer: a systematic review of longitudinal studies. Psychooncology. 2021;30(5):635–48. https://doi.org/10.1002/pon.5623.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Billiet T, Emsell L, Vandenbulcke M, Peeters R, Christiaens D, Leemans A, et al. Recovery from chemotherapy-induced white matter changes in young breast cancer survivors? Brain Imaging Behav. 2018;12(1):64–77. https://doi.org/10.1007/s11682-016-9665-8.

    Article  PubMed  Google Scholar 

  15. Ahles TA, Saykin AJ, McDonald BC, Li YL, Furstenberg CT, Hanscom BS, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol. 2010;28(29):4434–40. https://doi.org/10.1200/Jco.2009.27.0827.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wefel JS, Saleeba AK, Buzdar AU, Meyers CA. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer. 2010;116(14):3348–56. https://doi.org/10.1002/cncr.25098.

    Article  PubMed  Google Scholar 

  17. Koppelmans V, Breteler MMB, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol. 2012;30(10):1080–6. https://doi.org/10.1200/Jco.2011.37.0189.

    Article  PubMed  Google Scholar 

  18. Sardella A, Catalano A, Lenzo V, Bellone F, Corica F, Quattropani MC, et al. Association between cognitive reserve dimensions and frailty among older adults: a structured narrative review. Geriatr Gerontol Int. 2020;20(11):1005–23. https://doi.org/10.1111/ggi.14040.

    Article  PubMed  Google Scholar 

  19. Mandelblatt JS, Clapp JD, Luta G, Faul LA, Tallarico MD, McClendon TD, et al. Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance). Cancer. 2016;122(22):3555–63. https://doi.org/10.1002/cncr.30208.

    Article  PubMed  Google Scholar 

  20. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ, et al. Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp. 2011;32(8):1206–19. https://doi.org/10.1002/hbm.21102.

    Article  PubMed  Google Scholar 

  21. Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, et al. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat. 2007;103(3):303–11. https://doi.org/10.1007/s10549-006-9380-z.

    Article  CAS  PubMed  Google Scholar 

  22. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, Caan M, Douaud G, et al. Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Hum Brain Mapp. 2012;33(12):2971–83. https://doi.org/10.1002/hbm.21422.

    Article  PubMed  Google Scholar 

  23. Wefel JS, Schagen SB. Chemotherapy-related cognitive dysfunction. Curr Neurol Neurosci Rep. 2012;12(3):267–75. https://doi.org/10.1007/s11910-012-0264-9.

    Article  CAS  PubMed  Google Scholar 

  24. Cummings SR, Black DM, Nevitt MC, Browner WS, Cauley JA, Genant HK, et al. Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA. 1990;263(5):665–8.

    Article  CAS  PubMed  Google Scholar 

  25. Vogt MT, Cauley JA, Scott JC, Kuller LH, Browner WS. Smoking and mortality among older women - the study of osteoporotic fractures. Arch Intern Med. 1996;156(6):630–6. https://doi.org/10.1001/archinte.156.6.630.

    Article  CAS  PubMed  Google Scholar 

  26. Cauley JA, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR. Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group. JAMA. 1996;276(17):1404–8.

    Article  CAS  PubMed  Google Scholar 

  27. Grandits G and Neuhaus J. Using SAS® to perform individual matching in design of case-control studies https://support.sas.com/resources/papers/proceedings10/061-2010.pdf. in SAS Global Forum. 2010. Accessed 1 March 2022

  28. Folstein MF, Robins LN, Helzer JE. The Mini-Mental State Examination. Arch Gen Psychiatry. 1983;40(7):812. https://doi.org/10.1001/archpsyc.1983.01790060110016.

    Article  CAS  PubMed  Google Scholar 

  29. Arbuthnott K, Frank J. Trail making test, part B as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol. 2000;22(4):518–28. https://doi.org/10.1076/1380-3395(200008)22:4;1-0;Ft518.

    Article  CAS  PubMed  Google Scholar 

  30. Reitan RM. The relation of the trail making test to organic brain damage. J Consult Psychol. 1955;19(5):393–4. https://doi.org/10.1037/h0044509.

    Article  CAS  PubMed  Google Scholar 

  31. Blackwell T, Yaffe K, Ancoli-Israel S, Scheider JL, Cauley JA, Hillier TA, et al. Poor sleep is associated with impaired cognitive function in older women: the Study of Osteoporotic Fractures. Journals of Gerontology Series a-Biological Sciences and Medical Sciences. 2006;61(4):405–10. https://doi.org/10.1093/gerona/61.4.405.

    Article  PubMed  Google Scholar 

  32. Warton EM. Time after time: difference-in-differences and interrupted time series models in SAS. in SAS Global Forum 2020. 2020. https://www.sas.com/content/dam/SAS/support/en/sas-global-forum-proceedings/2020/4674-2020.pdf.

  33. Underwood EA, Rochon PA, Moineddin R, Lee PE, Wu W, Pritchard KI, et al. Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis. Breast Cancer Res Treat. 2018;168(2):299–310. https://doi.org/10.1007/s10549-017-4627-4.

    Article  CAS  PubMed  Google Scholar 

  34. Anstey KJ, Sargent-Cox K, Cherbuin N, Sachdev PS. Self-reported history of chemotherapy and cognitive decline in adults aged 60 and older: the PATH through life project. J Gerontol Ser a-Biol Sci Med Sci. 2015;70(6):729–35. https://doi.org/10.1093/gerona/glt195.

    Article  CAS  Google Scholar 

  35. Lange M, Heutte N, Rigal O, Noal S, Kurtz JE, Levy C, et al. Decline in cognitive function in older adults with early-stage breast cancer after adjuvant treatment. Oncologist. 2016;21(11):1337–48. https://doi.org/10.1634/theoncologist.2016-0014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kvale EA, Clay OJ, Ross-Meadows LA, McGee JS, Edwards JD, Unverzagt FW, et al. Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial. Eur J Cancer Care (Engl). 2010;19(1):110–7. https://doi.org/10.1111/j.1365-2354.2008.01018.x.

    Article  CAS  PubMed  Google Scholar 

  37. Dubois M, Lapinte N, Villier V, Lecointre C, Roy V, Tonon MC, et al. Chemotherapy-induced long-term alteration of executive functions and hippocampal cell proliferation: role of glucose as adjuvant. Neuropharmacology. 2014;79:234–48. https://doi.org/10.1016/j.neuropharm.2013.11.012.

    Article  CAS  PubMed  Google Scholar 

  38. Feng Y, Zhang XD, Zheng G, Zhang LJ. Chemotherapy-induced brain changes in breast cancer survivors: evaluation with multimodality magnetic resonance imaging. Brain Imaging Behav. 2019;13(6):1799–814. https://doi.org/10.1007/s11682-019-00074-y.

    Article  PubMed  Google Scholar 

  39. Andryszak P, Wilkosc M, Izdebski P, Zurawski B. A systemic literature review of neuroimaging studies in women with breast cancer treated with adjuvant chemotherapy. Contemp Oncol (Pozn). 2017;21(1):6–15. https://doi.org/10.5114/wo.2017.66652.

    Article  PubMed  Google Scholar 

  40. Bruno J, Hosseini SM, Kesler S. Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors. Neurobiol Dis. 2012;48(3):329–38. https://doi.org/10.1016/j.nbd.2012.07.009.

    Article  PubMed  PubMed Central  Google Scholar 

  41. van der Willik KD, Koppelmans V, Hauptmann M, Compter A, Ikram MA, Schagen SB. Inflammation markers and cognitive performance in breast cancer survivors 20 years after completion of chemotherapy: a cohort study. Breast Cancer Res. 2018;20(1):135. https://doi.org/10.1186/s13058-018-1062-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kesler S, Janelsins M, Koovakkattu D, Palesh O, Mustian K, Morrow G, et al. Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav Immun. 2013;30(Suppl):S109–16. https://doi.org/10.1016/j.bbi.2012.05.017.

    Article  CAS  PubMed  Google Scholar 

  43. Cheung YT, Ng T, Shwe M, Ho HK, Foo KM, Cham MT, et al. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study. Ann Oncol. 2015;26(7):1446–51. https://doi.org/10.1093/annonc/mdv206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhao JJ, Zuo H, Ding K, Zhang XQ, Bi ZR, Cheng HD. Changes in plasma IL-1 beta, TNF-alpha and IL-4 levels are involved in chemotherapy-related cognitive impairment in early-stage breast cancer patients. Am J Transl Res. 2020;12(6):3046–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bagnall-Moreau C, Chaudhry S, Salas-Ramirez K, Ahles T, Hubbard K. Chemotherapy-induced cognitive impairment is associated with increased inflammation and oxidative damage in the hippocampus. Mol Neurobiol. 2019;56(10):7159–72. https://doi.org/10.1007/s12035-019-1589-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fernandes HA, Richard NM, Edelstein K. Cognitive rehabilitation for cancer-related cognitive dysfunction: a systematic review. Support Care Cancer. 2019;27(9):3253–79. https://doi.org/10.1007/s00520-019-04866-2.

    Article  PubMed  Google Scholar 

  47. Von Ah D, Crouch A. Cognitive rehabilitation for cognitive dysfunction after cancer and cancer treatment: implications for nursing practice. Semin Oncol Nurs. 2020;36(1):150977. https://doi.org/10.1016/j.soncn.2019.150977.

    Article  Google Scholar 

  48. Campbell KL, Zadravec K, Bland KA, Chesley E, Wolf F, Janelsins MC. The effect of exercise on cancer-related cognitive impairment and applications for physical therapy: systematic review of randomized controlled trials. Phys Ther. 2020;100(3):523–42. https://doi.org/10.1093/ptj/pzz090.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Horowitz TS, Suls J, Trevino M. A call for a neuroscience approach to cancer-related cognitive impairment. Trends Neurosci. 2018;41(8):493–6. https://doi.org/10.1016/j.tins.2018.05.001.

    Article  CAS  PubMed  Google Scholar 

  50. Gavelin HM, Lampit A, Hallock H, Sabates J, Bahar-Fuchs A. Cognition-oriented treatments for older adults: a systematic overview of systematic reviews. Neuropsychol Rev. 2020;30(2):167–93. https://doi.org/10.1007/s11065-020-09434-8.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med. 2018;52(3):154-+. https://doi.org/10.1136/bjsports-2016-096587.

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to acknowledge the contribution of the Study of Osteoporotic Fractures (SOF) Investigators and the National Institute on Aging (NIA) AgingResearchBiobank (https://agingresearchbiobank.nia.nih.gov/) where the SOF collection of biospecimens and data is maintained.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN, 47405, USA

    Juhua Luo

  2. Park Nicollet Clinic and HealthPartners Institute, HealthPartners Inc, Minneapolis, MN, USA

    John T. Schousboe

  3. Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA

    John T. Schousboe

  4. Department of Medicine and Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    Kristine E. Ensrud

  5. Center for Care Delivery and Outcomes Research, VA Health Care System, Minneapolis, MN, USA

    Kristine E. Ensrud

  6. Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, IN, USA

    Michael Hendryx

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  1. Juhua Luo
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  4. Michael Hendryx
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Contributions

Juhua Luo: Conceptualization, methodology, formal analysis, writing–original draft, and writing-review and editing. John T. Schousboe: Methodology, and writing-review and editing. Kristine E. Ensrud: Methodology and writing-review and editing. Michael Hendryx: Conceptualization, methodology, and writing-review and editing.

Corresponding author

Correspondence to Juhua Luo.

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Ethics approval

The study was reviewed and approved by the Human Research Protection Program (HRPP) Office of Research Compliance – Indiana University, Protocol #: 2011885371.

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At each Study of Osteoporosis Fractures site, the institutional review boards approved the study. All participants provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki.

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The authors declare no competing interests.

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Luo, J., Schousboe, J.T., Ensrud, K.E. et al. Long-term changes of cognitive impairment among older breast cancer survivors. J Cancer Surviv 17, 1760–1768 (2023). https://doi.org/10.1007/s11764-022-01220-0

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