Association of pro-inflammatory cytokines and chemotherapy-associated cognitive impairment in breast

BACKGROUND:

Existing evidence suggests that pro-inflammatory cytokines play an intermediary role in post-chemotherapy cognitive impairment. This is one of the largest multi-centered, cohort studies conducted in Singapore to evaluate the prevalence and pro-inflammatory biomarkers associated with cognitive impairment in breast cancer patients.
PATIENTS AND METHODS:

Chemotherapy-receiving breast cancer patients (Stages I to III) were recruited. Pro-inflammatory plasma cytokines concentrations (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α) were evaluated at 3 time-points (prior to chemotherapy, 6 weeks 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% 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.

© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.