Associations of plasma brain-derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long-term cancer-related cognitive impairment in survivors of breast cancer

Breast Cancer Res Treat. 2020 Oct;183(3):683-696. doi: 10.1007/s10549-020-05807-y. Epub 2020 Jul 21.


Purpose: Brain-derived neurotrophic factor (BDNF) and the BDNF Val66Met polymorphism (rs6265) have been implicated in neurodegenerative conditions. This study aimed to investigate the associations of plasma BDNF and rs6265 with cancer-related cognitive impairment (CRCI) at the end of chemotherapy, and with persistent and delayed CRCI up to 24 months post chemotherapy, among survivors of early-stage breast cancer.

Methods: A multicenter, longitudinal study involving 174 breast cancer patients was conducted. CRCI was assessed using the FACT-Cog (V3) questionnaire and the CANTAB software. Plasma BDNF levels were quantified using an enzyme-linked immunosorbent assay at serial time points and genotyping was achieved using Sanger sequencing. The associations of BDNF and rs6265 with CRCI were analyzed using logistic regressions.

Results: A smaller magnitude of reduction in plasma BDNF between baseline and the end of chemotherapy was correlated with protection from overall subjective CRCI (OR 0.88; 95% CI 0.79-0.99). Furthermore, patients with higher plasma BDNF levels at the end of chemotherapy had lower odds of developing persistent overall subjective CRCI (OR 0.74; 95% CI 0.57-0.97) and persistent CRCI in the functional interference domain (OR 0.62; 95% CI 0.39-0.98). BDNF Met allele carriers were protected against subjective CRCI at the end of chemotherapy in the multitasking and memory domains, and against persistent subjective CRCI in the mental acuity and multitasking domains.

Conclusion: BDNF plasma level or rs6265 genotype information may facilitate the identification of patients at higher risk of long-term CRCI during survivorship and enable the implementation of early intervention strategies that increase BDNF levels.

Keywords: BDNF; Breast cancer; Cancer-related cognitive impairment; Survivorship; rs6265.

Publication types

  • Multicenter Study

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Cognitive Dysfunction* / genetics
  • Female
  • Genotype
  • Humans
  • Longitudinal Studies
  • Polymorphism, Single Nucleotide
  • Survivors


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human