Background: Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers, the long-term toxic effects of such therapy are a concern, Cognitive deficits (e,g,, problems with memory and concentration) are not uncommon after chemotherapy, but they have not been documented systematically, In this study, we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were randomly assigned to receive either high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, and we investigated whether high-dose chemotherapy impaired cognitive functioning more than standard-dose chemotherapy, Methods: Cognitive functioning was evaluated by use of a battery of neuropsychologic tests, In addition, patients were interviewed with regard to cognitive problems, health-related quality of life, anxiety, and depression, Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy (control patients), Results: The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen, 36 patients treated with standard-dose chemotherapy plus tamoxifen, and 34 control patients, For all patients, the average time since the completion of last nonhormonal therapy was 2 years, Cognitive impairment was found in 32% of the patients treated with high-dose chemotherapy, in 17% of the patients treated with standard-dose chemotherapy, and in 9% of the control patients, In comparison with the control patients, patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment (odds ratio; 95% confidence interval [CI] = 1.8-37.7); in comparison with the patients who received standard-dose chemotherapy, this risk of impairment was 3.5-times higher (95% CI = 1.0-12.8), Conclusion: High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy, Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.
