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.

Keywords: breast cancer; chemotherapy; cognitive changes; dose-response relationship; neuropsychological testing; oncology.