Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2019

Open Access 01-06-2019 | Breast Cancer | Epidemiology

The effect of chemotherapy on subjective cognitive function in younger early-stage breast cancer survivors treated with chemotherapy compared to older patients

Published in: Breast Cancer Research and Treatment | Issue 2/2019

Login to get access

Abstract

Purpose

To evaluate the impact of chemotherapy on subjective cognitive functioning according to age in a large cohort of breast cancer patients.

Methods

Within the UMBRELLA cohort, 715 patients with early-stage primary invasive breast cancer (T1-3N0-1M0) were selected. Subjective cognitive function was assessed by means of the EORTC QLQ-C30 up to 24 months and compared between patients treated with and without chemotherapy, for three different age strata (355 patients < 55 years, 240 patients aged 55–65 years, and 120 patients > 65 years). Differences between chemotherapy and non-chemotherapy patients by age at different time points were assessed by linear mixed-effect models correcting for age, tumor stage, educational level, endocrine therapy, anxiety, and depression.

Results

In total, 979 patients from the UMBRELLA cohort were included, of which 715 (73%) responded to baseline and at least one follow-up questionnaire. Questionnaire response rates ranged between 92 and 70%. The proportion of patients treated with chemotherapy decreased with age: 64% (n = 277) in patients < 55 years, 45% (n = 107) in patients 55–65 years, and 23% (n = 27) in patients > 65 years. Chemotherapy was associated with reduced subjective cognitive functioning. The impact of chemotherapy on subjective cognitive function was most pronounced in patients < 55 years, followed by those between 55 and 65 years. In the youngest age groups, patients treated with chemotherapy had significantly lower cognitive functioning up to 24 months. In women over 65 years, subjective cognitive functioning was comparable between patients treated with and without chemotherapy.

Conclusion

This study confirms that chemotherapy is associated with impaired subjective self-reported cognitive functioning in breast cancer patients, and the effect persists at least up to 2 years after diagnosis. The impact of chemotherapy on self-reported cognitive functioning in the first 24 months is most pronounced in younger patients, especially those under 55 years of age.
Appendix
Available only for authorised users
Literature
1.
go back to reference Holzel D, Eckel R, Bauerfeind I, Baier B, Beck T, Braun M et al (2017) Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the Munich Cancer Registry. J Cancer Res Clin Oncol 143(9):1701–1712CrossRefPubMed Holzel D, Eckel R, Bauerfeind I, Baier B, Beck T, Braun M et al (2017) Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the Munich Cancer Registry. J Cancer Res Clin Oncol 143(9):1701–1712CrossRefPubMed
2.
go back to reference Ganz PA, Kwan L, Castellon SA, Oppenheim A, Bower JE, Silverman DH et al (2013) Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance. J Natl Cancer Inst 105(11):791–801CrossRefPubMedPubMedCentral Ganz PA, Kwan L, Castellon SA, Oppenheim A, Bower JE, Silverman DH et al (2013) Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance. J Natl Cancer Inst 105(11):791–801CrossRefPubMedPubMedCentral
3.
go back to reference Boykoff N, Moieni M, Subramanian SK (2009) Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 3(4):223–232CrossRefPubMedPubMedCentral Boykoff N, Moieni M, Subramanian SK (2009) Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 3(4):223–232CrossRefPubMedPubMedCentral
4.
go back to reference Winocur G, Johnston I, Castel H (2018) Chemotherapy and cognition: International Cognition and Cancer Task Force recommendations for harmonising preclinical research. Cancer Treat Rev 69:72–83CrossRefPubMed Winocur G, Johnston I, Castel H (2018) Chemotherapy and cognition: International Cognition and Cancer Task Force recommendations for harmonising preclinical research. Cancer Treat Rev 69:72–83CrossRefPubMed
5.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444CrossRef Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444CrossRef
6.
go back to reference Wefel JS, Vardy J, Ahles T, Schagen SB (2011) International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12(7):703–708CrossRefPubMed Wefel JS, Vardy J, Ahles T, Schagen SB (2011) International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12(7):703–708CrossRefPubMed
7.
go back to reference Wefel JS, Saleeba AK, Buzdar AU, Meyers CA (2010) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 116(14):3348–3356CrossRefPubMed Wefel JS, Saleeba AK, Buzdar AU, Meyers CA (2010) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 116(14):3348–3356CrossRefPubMed
8.
go back to reference Pullens MJ, De Vries J, Van Warmerdam LJ, Van De Wal MA, Roukema JA (2013) Chemotherapy and cognitive complaints in women with breast cancer. Psychooncology 22(8):1783–1789CrossRefPubMed Pullens MJ, De Vries J, Van Warmerdam LJ, Van De Wal MA, Roukema JA (2013) Chemotherapy and cognitive complaints in women with breast cancer. Psychooncology 22(8):1783–1789CrossRefPubMed
9.
go back to reference Schagen SB, Muller MJ, Boogerd W, Rosenbrand RM, van Rhijn D, Rodenhuis S et al (2002) Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients. Ann Oncol 13(9):1387–1397CrossRefPubMed Schagen SB, Muller MJ, Boogerd W, Rosenbrand RM, van Rhijn D, Rodenhuis S et al (2002) Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients. Ann Oncol 13(9):1387–1397CrossRefPubMed
10.
go back to reference Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB (2012) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30(10):1080–1086CrossRefPubMed Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB (2012) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30(10):1080–1086CrossRefPubMed
11.
go back to reference Bray VJ, Dhillon HM, Vardy JL (2018) Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment. J Cancer Surviv 12(4):537–559CrossRefPubMed Bray VJ, Dhillon HM, Vardy JL (2018) Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment. J Cancer Surviv 12(4):537–559CrossRefPubMed
12.
go back to reference Young-Afat DA, van Gils CH, van den Bongard HJGD, Verkooijen HM, UMBRELLA Study Group (2017) The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA): objectives, design, and baseline results. Breast Cancer Res Treat 164(2):445–450CrossRefPubMedPubMedCentral Young-Afat DA, van Gils CH, van den Bongard HJGD, Verkooijen HM, UMBRELLA Study Group (2017) The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA): objectives, design, and baseline results. Breast Cancer Res Treat 164(2):445–450CrossRefPubMedPubMedCentral
13.
go back to reference Risicoprofilering Richtlijn Mammacarcinoom (2012) Kwaliteitsinstituut voor de gezondheidszorg CBO VvIK, pp 81–83 Risicoprofilering Richtlijn Mammacarcinoom (2012) Kwaliteitsinstituut voor de gezondheidszorg CBO VvIK, pp 81–83
15.
go back to reference Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376CrossRefPubMed Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376CrossRefPubMed
16.
go back to reference Spinhoven P, Ormel J, Sloekers PP, Kempen GI, Speckens AE, Van Hemert AM (1997) A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychol Med;27(2):363–370CrossRefPubMed Spinhoven P, Ormel J, Sloekers PP, Kempen GI, Speckens AE, Van Hemert AM (1997) A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychol Med;27(2):363–370CrossRefPubMed
17.
go back to reference Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370CrossRefPubMed Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370CrossRefPubMed
18.
go back to reference Smith AB, Selby PJ, Velikova G, Stark D, Wright EP, Gould A et al (2002) Factor analysis of the Hospital Anxiety and Depression Scale from a large cancer population. Psychol Psychother 75(Pt 2):165–176CrossRefPubMed Smith AB, Selby PJ, Velikova G, Stark D, Wright EP, Gould A et al (2002) Factor analysis of the Hospital Anxiety and Depression Scale from a large cancer population. Psychol Psychother 75(Pt 2):165–176CrossRefPubMed
20.
go back to reference van de Poll-Franse LV, Horevoorts N, van Eenbergen M, Denollet J, Roukema JA, Aaronson NK et al (2011) The Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship registry: scope, rationale and design of an infrastructure for the study of physical and psychosocial outcomes in cancer survivorship cohorts. Eur J Cancer 47(14):2188–2194CrossRefPubMed van de Poll-Franse LV, Horevoorts N, van Eenbergen M, Denollet J, Roukema JA, Aaronson NK et al (2011) The Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship registry: scope, rationale and design of an infrastructure for the study of physical and psychosocial outcomes in cancer survivorship cohorts. Eur J Cancer 47(14):2188–2194CrossRefPubMed
21.
go back to reference Fayers PM, Aaronson NK (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European Organisation for Research and Treatment of Cancer, Brussels Fayers PM, Aaronson NK (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European Organisation for Research and Treatment of Cancer, Brussels
22.
go back to reference Bonnetain F, Fiteni F, Efficace F, Anota A (2016)Statistical challenges in the analysis of health-related quality of life in cancer clinical trials. J Clin Oncol 34(16):1953–1956CrossRefPubMed Bonnetain F, Fiteni F, Efficace F, Anota A (2016)Statistical challenges in the analysis of health-related quality of life in cancer clinical trials. J Clin Oncol 34(16):1953–1956CrossRefPubMed
23.
go back to reference ’Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum, Hillsdale ’Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum, Hillsdale
24.
go back to reference Bedard G, Zeng L, Lam H, Cella D, Zhang L, Lauzon N et al (2012) Meaningful change in oncology quality-of-life instruments: a systematic literature review. Expert Rev Pharmacoecon Outcomes Res 12(4):475–483CrossRefPubMed Bedard G, Zeng L, Lam H, Cella D, Zhang L, Lauzon N et al (2012) Meaningful change in oncology quality-of-life instruments: a systematic literature review. Expert Rev Pharmacoecon Outcomes Res 12(4):475–483CrossRefPubMed
25.
go back to reference Raman S, Ding K, Chow E, Meyer RM, van der Linden YM, Roos D et al (2018) Minimal clinically important differences in the EORTC QLQ-C30 and brief pain inventory in patients undergoing re-irradiation for painful bone metastases. Qual Life Res 27(4):1089–1098CrossRefPubMed Raman S, Ding K, Chow E, Meyer RM, van der Linden YM, Roos D et al (2018) Minimal clinically important differences in the EORTC QLQ-C30 and brief pain inventory in patients undergoing re-irradiation for painful bone metastases. Qual Life Res 27(4):1089–1098CrossRefPubMed
26.
go back to reference Jung MS, Zhang M, Askren MK, Berman MG, Peltier S, Hayes DF et al (2017) Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis. Brain Imaging Behav 11(1):86–97CrossRefPubMed Jung MS, Zhang M, Askren MK, Berman MG, Peltier S, Hayes DF et al (2017) Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis. Brain Imaging Behav 11(1):86–97CrossRefPubMed
27.
go back to reference Quesnel C, Savard J, Ivers H (2009) Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 116(1):113–123CrossRefPubMed Quesnel C, Savard J, Ivers H (2009) Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 116(1):113–123CrossRefPubMed
28.
go back to reference Janelsins MC, Heckler CE, Peppone LJ, Kamen C, Mustian KM, Mohile SG et al (2017) Cognitive complaints in survivors of breast cancer after chemotherapy compared with age-matched controls: an analysis from a nationwide, multicenter, prospective longitudinal study. J Clin Oncol 35(5):506–514CrossRefPubMed Janelsins MC, Heckler CE, Peppone LJ, Kamen C, Mustian KM, Mohile SG et al (2017) Cognitive complaints in survivors of breast cancer after chemotherapy compared with age-matched controls: an analysis from a nationwide, multicenter, prospective longitudinal study. J Clin Oncol 35(5):506–514CrossRefPubMed
30.
go back to reference Mandelblatt JS, Clapp JD, Luta G, Faul LA, Tallarico MD, McClendon TD et al (2016) Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance). Cancer 2016 122(22):3555–3563 Mandelblatt JS, Clapp JD, Luta G, Faul LA, Tallarico MD, McClendon TD et al (2016) Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance). Cancer 2016 122(22):3555–3563
31.
go back to reference Debess J, Riis JO, Engebjerg MC, Ewertz M (2010) Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Res Treat 121(1):91–100CrossRefPubMed Debess J, Riis JO, Engebjerg MC, Ewertz M (2010) Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Res Treat 121(1):91–100CrossRefPubMed
32.
go back to reference Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS et al (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 28(29):4434–4440CrossRefPubMedPubMedCentral Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS et al (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 28(29):4434–4440CrossRefPubMedPubMedCentral
33.
go back to reference Hurria A, Hurria A, Zuckerman E, Panageas KS, Fornier M, D’Andrea G et al (2006) A prospective, longitudinal study of the functional status and quality of life of older patients with breast cancer receiving adjuvant chemotherapy. J Am Geriatr Soc 54(7):1119–1124CrossRefPubMed Hurria A, Hurria A, Zuckerman E, Panageas KS, Fornier M, D’Andrea G et al (2006) A prospective, longitudinal study of the functional status and quality of life of older patients with breast cancer receiving adjuvant chemotherapy. J Am Geriatr Soc 54(7):1119–1124CrossRefPubMed
34.
go back to reference Healey MK, Campbell KL, Hasher L (2008) Cognitive aging and increased distractibility: costs and potential benefits. Prog Brain Res 169:353–363CrossRefPubMed Healey MK, Campbell KL, Hasher L (2008) Cognitive aging and increased distractibility: costs and potential benefits. Prog Brain Res 169:353–363CrossRefPubMed
35.
go back to reference Vega JN, Dumas J, Newhouse PA (2018) Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause. Psychooncology 27(9):2198–2205CrossRefPubMedPubMedCentral Vega JN, Dumas J, Newhouse PA (2018) Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause. Psychooncology 27(9):2198–2205CrossRefPubMedPubMedCentral
36.
go back to reference Ahles TA, Root JC, Ryan EL (2012) Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. J Clin Oncol 30(30):3675–3686CrossRefPubMedPubMedCentral Ahles TA, Root JC, Ryan EL (2012) Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. J Clin Oncol 30(30):3675–3686CrossRefPubMedPubMedCentral
38.
go back to reference Mandelblatt JS, Jacobsen PB, Ahles T (2014) Cognitive effects of cancer systemic therapy: implications for the care of older patients and survivors. J Clin Oncol 32(24):2617–2626CrossRefPubMedPubMedCentral Mandelblatt JS, Jacobsen PB, Ahles T (2014) Cognitive effects of cancer systemic therapy: implications for the care of older patients and survivors. J Clin Oncol 32(24):2617–2626CrossRefPubMedPubMedCentral
39.
go back to reference Schilder CM, Eggens PC, Seynaeve C, Linn SC, Boogerd W, Gundy CM et al (2009) Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol 48(1):76–85CrossRefPubMed Schilder CM, Eggens PC, Seynaeve C, Linn SC, Boogerd W, Gundy CM et al (2009) Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol 48(1):76–85CrossRefPubMed
40.
go back to reference Mandelblatt JS, Clapp JD, Luta G, Faul LA, Tallarico MD, McClendon TD et al (2016) Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance). Cancer 122(22):3555–3563 22CrossRefPubMed Mandelblatt JS, Clapp JD, Luta G, Faul LA, Tallarico MD, McClendon TD et al (2016) Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance). Cancer 122(22):3555–3563 22CrossRefPubMed
41.
go back to reference Nicolini A, Ferrari P, Duffy MJ (2018) Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol 52(Pt 1):56–73CrossRefPubMed Nicolini A, Ferrari P, Duffy MJ (2018) Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol 52(Pt 1):56–73CrossRefPubMed
42.
go back to reference Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S et al (2016) 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375(8):717–729CrossRefPubMed Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S et al (2016) 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375(8):717–729CrossRefPubMed
43.
go back to reference Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF et al (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014CrossRefPubMedPubMedCentral Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF et al (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014CrossRefPubMedPubMedCentral
44.
go back to reference Jacobs W, Das E, Schagen SB (2017) Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness. Psychol Health 32(1):78–93CrossRefPubMed Jacobs W, Das E, Schagen SB (2017) Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness. Psychol Health 32(1):78–93CrossRefPubMed
Metadata
Title
The effect of chemotherapy on subjective cognitive function in younger early-stage breast cancer survivors treated with chemotherapy compared to older patients
Publication date
01-06-2019
Published in
Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05149-4

Other articles of this Issue 2/2019

Breast Cancer Research and Treatment 2/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine