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Journal of Clinical Oncology, Vol 24, No 32 (November 10), 2006: pp. 5170-5171 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.07.8303
Does Cognitive Impairment After Chemotherapy for Breast Cancer Improve Over Time or Does Practice Make Perfect?Department of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands To the Editor: There is increasing interest in cognitive deficits after chemotherapy. Several neuropsychological studies have indicated the occurrence of cognitive impairment in a number of patients treated with chemotherapy based on data of predominantly breast cancer patients.1-12 Most of these studies are retrospective and consist of small and heterogeneous samples. As a consequence, few methodologically rigorous studies exist to guide clinical practice, and thus, there is a need for large scale prospective studies on the association between chemotherapy and cognitive functioning. Given this state of affairs, the study published in the Journal of Clinical Oncology in November 2005 by Mar Fan et al13 was both relevant and opportune. The study presents the results of a 1- and 2-year neuropsychological follow-up examination of the impact of adjuvant chemotherapy on cognitive function in breast cancer patients after an initial baseline assessment during treatment. The study's central conclusion is that cognitive dysfunction as an adverse effect of chemotherapy improves over time. Due to the current absence of comparable large prospective studies on this subject, it is likely that many researchers, health care providers, and patients alike will attach great significance to these results. Unfortunately, we have some serious concerns regarding the methodology used in the study. Specifically, we wonder whether the observed improvement in cognitive functioning could be attributed to positive practice effects, which are rather common in neuropsychological research. The fact that the authors did not control for such effects is a bit perplexing, given more recent information—provided by the authors themselves—indicating that the instrument they used to assess cognitive dysfunction is highly sensitive to effects of practice. In the following discussion we will try to make this point clear. In their JCO study, the authors used the High Sensitive Cognitive Screen (HSCS)14 to evaluate the incidence and the course of cognitive impairment after chemotherapy. The HSCS classified 16% of patients as moderate-severely cognitively impaired during cytotoxic treatment. This percentage decreased to 4.4% after 1 year and to 3.8% after 2 years. In a healthy control group tested at similar time intervals, the percentage of impaired subjects decreased from 5% at baseline, to 3.6% and 0% at 1 and 2 years, respectively. From this information the authors concluded that the adverse effect of chemotherapy improves in most patients. Recently, the same group published a study in Supportive Care and Cancer in which the suitability of the HSCS was examined for use in longitudinal designs.15 In this study cognitive functioning was assessed in a comparable sample of breast cancer patients who were either still on chemotherapy or had completed it within the previous 2 years. In this latter study, the HSCS classified 30% of the patients as being moderate-severely cognitively impaired at baseline. Patients were retested twice, with an interval of, on average, 17 days (range, 7 to 90 days). The percentage of impaired patients decreased to 5% on both the first and second retest. Two observations immediately stand out. First, the prevalence of cognitive impairment in the comparable research population used in the latter study nearly doubles the prevalence found in the former study, thus casting some doubts on the general validity of the HSCS. Second, the cognitive dysfunction found in the latter study improved at a rate greatly exceeding the improvement found in the former study. The authors concluded that the rapid decrease in the number of chemotherapy patients with moderate-severe cognitive impairment is highly likely due to practice effects, and they recommend not using the HSCS for longitudinal studies with short intervals. Although the retest interval for patients (7 to 90 days) in the latter article is much shorter than the retest interval in the prospective study (1 year), the occurrence of positive practice effects, even in the case of a delay of 12 months between testing, is quite common in neuropsychological research. In a study by Salthouse et al16 it was shown that, for adults between 18 and 60 years of age, 7 or more years were needed before positive retest effects were no longer detectable on neuropsychological testing. In the prospective study by Mar Fan et al no adjustment for practice effects was carried out, even though the performance of the healthy controls showed a clear improvement; none of the controls was classified as moderate-severely impaired 2 years later. Given the recently obtained information provided by the same authors on the occurrence of strong practice effects in the HSCS in chemotherapy patients, we question the prospective study's reassuring conclusion that cognitive dysfunction after chemotherapy decreases over time. We wonder whether this conclusion would still hold when a correction for practice effects is carried out. Late complications of cancer treatments are increasingly important because curative treatments are available for substantial groups of cancer patients. Women with a history of breast cancer treated with chemotherapy constitute a large part of the cancer survivor community. Adverse effects on cognition are of great concern to these women and many monitor the scientific literature on this topic closely. In the light of the importance of the Mar Fan study and its potential implications for intervention, we hope that the researchers will take our concerns seriously, and undertake a reanalysis of their prospective data with correction for practice effects. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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