Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study

Abstract

Background: Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce.

Patients and methods: This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted.

Results: We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P < .001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P < .001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients.

Conclusion: Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.

Keywords: CICI; breast cancer; cognitive; impairment; neurotoxicity; quality of life.

Figure 1.

CONSORT diagram. Flow chart of the patients included in the study and their distribution within the study points with representation of dropouts.

Figure 2.

Results of the cognitive domains of the neuropsychological assessment. The results of verbal memory (A), figural memory (B), executive function (C), and attention (D), as well as a total cognitive score (E) are presented as individual change from baseline, both for the first follow-up 2-4 weeks after completion of chemotherapy (V2−V1) and the long-term follow-up after 2-3 years (V3−V1). The medians and the interquartile ranges are presented for each domain for the chemotherapy and the control groups. If there is a statistically significant difference between the groups or a P-value close to significance, these are displayed. Abbreviations: ROCF: Rey-Osterrieth Complex Figure Test; TMT: Trail Marking Test; VLMT: Verbal Learning and Memory Test.

Figure 3.

Test results of the quality of life questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC-QLQ-BR23). The results of physical functioning (A), cognitive functioning (B), social functioning (C), systemic therapy side effects (D), fatigue (E), pain (F), insomnia (G), and Global Health (E) are presented as individual change from baseline, both for the first follow-up 2-4 weeks after completion of chemotherapy (V2−V1) and the long-term follow-up after 2-3 years (V3−V1). The medians and the interquartile ranges are presented for each scale for the chemotherapy and the control groups. If there is a statistically significant difference between the groups or a P-value close to significance, these are displayed.

Figure 4.

Serum concentrations of the neurodegenerative markers and their correlation with total cognitive function. For the neurodegenerative markers NfL, tau protein, GFAP, and pNfH, the serum concentrations (in pg/mL) including the medians and interquartile ranges for the chemotherapy and control groups are presented as individual changes from the first follow-up 2-4 weeks after completion of chemotherapy compared to baseline (V2−V1). In addition, the correlation analysis between the change in serum concentrations of NfL and pNfH and total cognitive function are presented. If there is a significant difference between the groups/a significant correlation or a P-value close to statistical significance, these are displayed. Abbreviations: GFAP, glial fibrillary acidic protein; NfL, Neurofilament light chain; pNfH, phosphorylated neurofilament heavy chain.