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

Oncologist. 2025 Feb 6;30(2):oyae268. doi: 10.1093/oncolo/oyae268.

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.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Chemotherapy-Related Cognitive Impairment* / diagnosis
  • Chemotherapy-Related Cognitive Impairment* / etiology
  • Chemotherapy-Related Cognitive Impairment* / physiopathology
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / physiopathology
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Neuropsychological Tests
  • Prospective Studies
  • Quality of Life