Association of pro-inflammatory biomarkers and post-chemotherapy cognitive changes in Asian breast cancer patients: A prospective cohort study.

Abstract

9506 Background: Although existing evidence suggests that cytokines play an intermediary role in the development of post-chemotherapy cognitive changes, specific cytokines associated with this neurotoxic sequela of chemotherapy are still unknown. This study was designed to identify pro-inflammatory biomarkers that are associated with memory and attention impairment in Asian patients receiving chemotherapy. Methods: This is a prospective, cohort study conducted at the National Cancer Centre Singapore. Early-stage Asian breast cancer patients (Stage I to III), who received anthracycline and/or taxane-based chemotherapy were recruited. Computerized neuropsychological assessments (Headminder) were administered to evaluate patients’ memory and attention performances and a panel of pro-inflammatory plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α) was evaluated using multiplex immunoassay at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Memory and attention impairment were defined as a >2.5 reduction of the Zscore from baseline, as calculated by the reliable change index for repeated cognitive measurements. Results: Thirty-six patients were included (mean age 49.7±9.0 years; 80.6% Chinese). Comparing to T1, 50.0% and 36.1% of the patients suffered memory and attention impairment at T3, respectively. Comparing patients with intact memory to those who suffered impairment from T2 to T3, they had higher levels of circulating IL-1β [median (IQR): 0.44 (0.1-0.5) vs 0.56 (0.4-0.7) pg/ml, p=0.069], IL-4 [0.41 (0.0-0.8) vs 0.85 (0.2-1.5) pg/ml, p=0.067) and TNF-α [1.78 (1.3-2.2) vs 3.01 (1.3-3.5) pg/ml, p=0.069]. At T3, reduction of attention scores were associated with higher levels of IL-1β (rs= -0.37, p=0.023) and IL-6 (rs= -0.33, p=0.045). No significant associations were identified with IL-2, IL-8, IL-10, GM-CSF and IFN-γ. Conclusions: These findings suggest that an increase in the post-chemotherapy levels of TNF-α, IL-1β, IL-4 and IL-6 may have an association with the manifestations of memory and attention impairment in Asian breast cancer patients.