title: Potential role of pNF-H, a biomarker of axonal damage in the central nervous system, as a predictive marker of chemotherapy-induced cognitive impairment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Seventy-six patients with early breast cancer in various phases of treatment (naïve 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 χ(2) 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-naïve 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.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Natori
authors.affiliation: Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sumitani
authors.affiliation: Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Kogure
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Yamauchi
authors.affiliation: Department of Breast Surgery, St. Luke's International Hospital, Tokyo, Japan. hideyama@luke.ac.jp.
authors.forename: Hideko
authors.initials: H
authors.lastname: Yamauchi
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy*; D002490:Central Nervous System / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood*; D009483:Neuropsychological Tests; D010766:Phosphorylation
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H