Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Purpose: Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. Experimental Design: Seventy-six patients with early breast cancer in various phases of treatment (naive to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The c2 and Mann-Whitney tests were used for statistical analysis. Results: Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naive patients or patients with a history of chemotherapy. The pNF-H-positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups. Conclusions: The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy. (C) 2015 AACR.