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Ann Oncol. 2015 Jul;26(7):1446-51. doi: 10.1093/annonc/mdv206. Epub 2015 Apr 28.

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

Author information

1
Department of Pharmacy, National University of Singapore, Singapore Department of Pharmacy, National Cancer Centre Singapore, Singapore.
2
Department of Pharmacy, National University of Singapore, Singapore.
3
Department of Pharmacy.
4
Breast Centre, KK Women's and Children's Hospital, Singapore.
5
Departments of Psychosocial Oncology, National Cancer Centre Singapore, Singapore.
6
Surgical Oncology, National Cancer Centre Singapore, Singapore.
7
Medical Oncology, National Cancer Centre Singapore, Singapore.
8
Medical Oncology, National Cancer Centre Singapore, Singapore Clinical Sciences, DUKE-NUS Graduate Medical School, Singapore, Singapore.
9
Department of Pharmacy, National University of Singapore, Singapore Department of Pharmacy, National Cancer Centre Singapore, Singapore Clinical Sciences, DUKE-NUS Graduate Medical School, Singapore, Singapore phaac@nus.edu.sg.

Abstract

BACKGROUND:

Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.

PATIENTS AND METHODS:

Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.

RESULTS:

Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).

CONCLUSIONS:

While elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

KEYWORDS:

FACT-Cog; breast cancer; chemobrain; cognitive disturbance; cognitive impairment; cytokines

PMID:
25922060
PMCID:
PMC4478978
DOI:
10.1093/annonc/mdv206
[Indexed for MEDLINE]
Free PMC Article

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