A large meta-analysis recently concluded that breast cancer patients are at risk for mild cognitive impairment after chemotherapy treatment. The findings were published in the latest issue of the Journal of Clinical Oncology. “In general, cognitive dysfunction after chemotherapy is mild and limited to verbal abilities, such as wording, and spatial visual abilities, such as getting lost easily in unfamiliar environments,” said Heather Jim, PhD, lead author of the paper and director of the H. Lee Moffitt Cancer Center in Florida. Center’s Institute for Health Outcomes and Behavioral Programs in Florida. The investigators claim current data show significant cognitive dysfunction in patients during treatment, but data on the long-term persistence of symptoms are controversial. The study was designed to explore relevant performance in patients in the post-chemotherapy phase. The target population was restricted to breast cancer patients, as most studies of post-chemotherapy cognitive function have been conducted on breast cancer patients. Dr. Jim and her colleagues analyzed 17 studies, 807 breast cancer patients who had received chemotherapy, including 391 breast cancer patients treated with local or endocrine therapy and 291 subjects without cancer. four studies conducted longitudinal comparisons of chemotherapy patients, six studies compared chemotherapy patients with patients who received only local therapy, three studies compared chemotherapy patients with non-cancer patients, and the remaining studies Multiple comparisons were conducted. The researchers classified the subjects based on neuropsychological test results with reference to major types of cognitive functioning. Measures included attention, executive ability (planning and putting into practice), motor acceleration, verbal ability, information processing, visuospatial ability, and visual memory. The investigators found a significant deterioration in cognitive functions such as verbal and visuospatial abilities in breast cancer chemotherapy patients compared to those without chemotherapy (all P < .01). There was a trend toward a non-significant deterioration in executive ability. No differences were seen in other measured parameters related to cognitive function. Further analysis showed that verbal ability outcomes were significantly worse in chemotherapy-treated patients compared with non-cancer control patients, but not compared with patients' own pre-chemotherapy baseline or compared with non-chemotherapy patients. The study design similarly found statistically significant differences in visuospatial ability outcomes. Patients with chemotherapy for breast cancer generally had significantly worse outcomes on these measures compared to patients without chemotherapy, but no differences were seen compared to patients' own pre-chemotherapy baseline or to non-cancer control patients. In addition, speech and visuospatial ability outcomes were not affected by age, education, time since chemotherapy, or endocrine therapy. "The standard deviations for the verbal ability and visuospatial ability effects were ?0.210 and ?0.291, respectively," Jim said. "For the quantification of cognitive impairment, we based our rule of thumb on a standard deviation of < 0.3 for mild, 0.5 for moderate, and > 0.7 for severe. Clinically, it means that in terms of verbal ability, the average (on average) breast cancer chemotherapy patient is 58% worse off than a non-chemothered breast cancer patient, and in terms of visuospatial ability, 61% worse off. The possibility of underestimation Dr. Jim believes that the highlights of this study are the large sample size, its selection of the post-chemotherapy phase, the superior methods of analysis of recent studies compared to previous studies (e.g., longitudinal comparative design and identification of cognitive function measures), and the inclusion of studies that were not included in previous meta-analyses. Compared with data from four previous meta-analyses, this study showed more and more diffuse cognitive dysfunction in patients with breast and other cancers. The authors concluded that the results of this meta-analysis, which focused on the post-chemotherapy phase, suggest that the degree of cognitive impairment in breast cancer patients from chemotherapy remains relatively mild compared to other types of antitumor therapies (active treatment phase). ”The main weakness of this meta-analysis is that it only gives information about patients in general, and there should be more heterogeneity in cognitive function after chemotherapy,” Jim said. In addition, the study’s findings from breast cancer patients may not be applicable to other types of cancer. “The effects of impaired cognitive function derived from studies that refer to all types of cancer may be smaller than those concluded in a single study because analysis of trial pools would ignore the assessment of individual patient risk factors,” said Tim Ahles, PhD, director of the Sloan-Kettering Cancer Center Neurology Director of the Research Unit at Sloan-Kettering Cancer Center in New York. “Identifying the population under study helps in understanding and deriving clinically useful answers.” However, Dr. Ahles believes this study brings good news for long-term care for all populations. Clinical Implications Dr. Ahles, co-author of the accompanying journal surgery review, noted that many investigators believe that specific subgroups of patients are at higher risk for significant cognitive dysfunction (J Clin Oncol. 2012;30:3568-3569). Previous studies have shown that greater age and lower retention of cognitive function (as measured by factors such as education, occupation, and cognitive stimulation) are risk factors for significant cognitive impairment. The results of this study did not confirm these, but the authors acknowledge that the majority of subjects were young, middle-aged patients with high levels of education. In addition, the review concludes that recent studies point to genetic factors that may increase susceptibility to cognitive dysfunction, including apolipoprotein E and catechol methyltransferase. “We are actively conducting research on genetic predictors of side effects of cancer treatment,” Dr. Jim said. “Our goal is to diagnose high-risk patients before they develop clinical problems so we can provide them with early intervention and treatment.” In general, patients are expected to show improvements in cognitive function over a 6-month period after chemotherapy, the investigators noted, and this improvement is variable, with some patients complaining of much more improvement than others. Patient complaints of improvement should be put to the neuropsychological assessment and evaluation of treatment strategies. “Patients are anxious for a quick recovery,” Dr. Ahles said. “It is important to tell patients that it will take six to 12 months to recover from the impaired cognitive function caused by chemotherapy. If the patient’s symptoms persist, then treatment needs to be given accordingly and individualized to the patient with changes.” Dr. Ahles believes the side effects in terms of impaired cognitive function should be considered in the larger context of treatment. “I often hear patients express to me concerns about cognitive function side effects,” he added. “I encourage them not to reject the appropriate treatment modality because of concerns in this area. Eliminating relapse is the most important thing.”