title: Cognitive effects of chemotherapy in breast cancer patients: a dose-response study.
abstract: OBJECTIVE
  The purpose of this study was to determine if cognition progressively worsens with cumulative chemotherapy exposure. We reasoned that the demonstration of such a 'dose-response' relationship would help to establish whether cognitive changes are caused by neurotoxic effects of chemotherapy or whether they are due to other confounding factors such as mood and pre-treatment differences in cognition.
  
  
  METHODS
  Sixty women with early stage breast cancer, aged 65 years or younger with no previous history of cancer or chemotherapy, were matched to 60 healthy women on age and education. Neuropsychological assessment was conducted after surgery but prior to commencing chemotherapy and then again following each chemotherapy cycle in patients and at yoked intervals in healthy controls. We used multilevel modeling to assess change over time in an overall cognitive summary score as well as domain-specific cognitive scores.
  
  
  RESULTS
  After controlling for baseline performance, age, education, and mood, the chemotherapy group showed a significant progressive decline over time relative to a matched healthy control group in an overall cognitive summary score, as well as in working memory, processing speed, verbal memory, and visual memory scores. A linear model best fit the trajectory of cognitive change over the course of treatment in the chemotherapy group supporting a dose-response hypothesis.
  
  
  CONCLUSIONS
  These results are in keeping with a dose-response relationship and provide the most compelling clinical evidence to date that cognitive decline is caused by chemotherapy exposure.
authors.affiliation: Ottawa Hospital - Civic Campus, Ottawa, ON, Canada. bcollins@ottawahospital.on.ca
authors.forename: Barbara
authors.initials: B
authors.lastname: Collins
authors.forename: Joyce
authors.initials: J
authors.lastname: MacKenzie
authors.forename: Giorgio A
authors.initials: GA
authors.lastname: Tasca
authors.forename: Carole
authors.initials: C
authors.lastname: Scherling
authors.forename: Andra
authors.initials: A
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000523:psychology; D016022:Case-Control Studies; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D055361:Multilevel Analysis; D009483:Neuropsychological Tests; D011795:Surveys and Questionnaires; D055815:Young Adult