Barbara Collins

A Meta-Analysis of the Neuropsychological Effects of Adjuvant Chemotherapy Treatment in Women Treated for Breast Cancer

ABSTRACT Given the improvement in mortality rates associated with breast cancer, the importance of understanding the long-term neuropsychological consequences of chemotherapy is becoming increasingly vital. This study applies meta-analytic techniques to the scant literature on the relationship between contemporary adjuvant chemotherapy treatment for breast cancer and cognitive dysfunction as examined through neuropsychological indices. Seven studies (involving more than 300 participants) were selected from over 200 potential articles, based on three inclusion criteria: presence of breast cancer, administration of chemotherapy treatment, and use of neuropsychological tests. From these, nine treatment-control comparisons were used to generate 129 Hedges d effect sizes across the cognitive domains of simple attention, working memory short- and long-term memory, speed of processing, language, spatial abilities, and motor function. Small to medium cumulative effect sizes, showing diminished cognitive function for chemotherapy treatment groups compared to control groups, were obtained for each of the eight cognitive domains. Overall, these results suggest that women who undergo adjuvant chemotherapy as treatment for breast cancer may experience subtle yet consequential cognitive decline.

Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment.

Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitive disturbances in some women, but the course is unclear. The current study evaluated the cognitive effects of adjuvant chemotherapy in post‐menopausal breast cancer patients 1 year following completion of treatment.

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients.

Pre-Chemotherapy Differences in Visuospatial Working Memory in Breast Cancer Patients Compared to Controls: An fMRI Study

Introduction: Cognitive deficits are a side-effect of chemotherapy, however pre-treatment research is limited. This study examines neurofunctional differences during working memory between breast cancer (BC) patients and controls, prior to chemotherapy. Methods: Early stage BC females (23), scanned after surgery but before chemotherapy, were individually matched to non-cancer controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing a Visuospatial N-back task and data was analyzed by multiple group comparisons. fMRI task performance, neuropsychological tests, hospital records, and salivary biomarkers were also collected. Results: There were no significant group differences on neuropsychological tests, estrogen, or cortisol. Patients made significantly fewer commission errors but had less overall correct responses and were slower than controls during the task. Significant group differences were observed for the fMRI data, yet results depended on the type of analysis. BC patients presented with increased activations during working memory compared to controls in areas such as the inferior frontal gyrus, insula, thalamus, and midbrain. Individual group regressions revealed a reverse relationship between brain activity and commission errors. Conclusion: This is the first fMRI investigation to reveal neurophysiological differences during visuospatial working memory between BC patients pre-chemotherapy and controls. These results also increase the knowledge about the effects of BC and related factors on the working memory network. Significance: This highlights the need to better understand the pre-chemotherapy BC patient and the effects of associated confounding variables.

Measuring neuropsychological change following breast cancer treatment: an analysis of statistical models.

This article considers the quantitative techniques currently in use in the evaluation of cognitive impairments associated with chemotherapy treatment for breast cancer. To illustrate differences among analytical approaches, all analyses were applied to baseline and posttreatment scores on neuropsychological tests obtained from Stages I and II breast cancer patients receiving either chemotherapy or hormonal therapy; a healthy control group with similar demographics to those of the treatment groups was also included. Conventional group analyses were compared with individual-based analyses (standardized regression-based and reliable change methods). Both univariate and multivariate techniques with and without covariates produced negligible effects. In contrast, results of the individual-based analyses identified a subset of participants in the chemotherapy group who experienced a severe decline in function on two or more tests. Differences between the control and treatment groups were greater than differences between the treatment groups alone. The standardized regression-based approach was more sensitive than the reliable change index in detecting chemotherapy and hormonal therapy subjects whose performance was different from baseline scores on two or more tests (roughly 80% vs. 50% of participants). From a clinical perspective, the degree of impairment determined on the basis of the individual-based methodologies could have a major impact on quality of life for those affected. On the whole, we argue that the standardized regression-based approach, allowing for the assessment of individual practice effects and evaluation of moderator variables, is the method of choice in this context.

Persistent cognitive changes in breast cancer patients 1 year following completion of chemotherapy.

Numerous studies have shown that there are acute cognitive side-effects of chemotherapy for breast cancer. Presumably, patients are more concerned about chronic treatment effects. This report from a prospective longitudinal study compares cognitive functioning in 56 breast cancer patients 1 year after chemotherapy to that of 56 healthy individuals. Neuropsychological test scores were combined into verbal memory, visual memory, working memory, and processing speed scores, as well as an overall summary score, and analyzed using multi-level growth modeling. Frequency of cognitive decline was assessed using regression-based change scores. There was significant rebound in the overall summary score from end of treatment to 1-year follow-up as well as a substantial reduction in the frequency of cognitive decline. However, more than one-third of the breast cancer patients who showed cognitive decline immediately following completion of chemotherapy showed persistent cognitive decline 1 year later. Furthermore, recovery was not seen in all cognitive domains. In fact, the rebound was significant only for working memory. Longer multi-site studies are recommended to explore the risk factors for and the permanence of these longer-term cognitive effects.

Study of the cognitive effects of chemotherapy: considerations in selection of a control group.

Neuropsychological data collected in 28 breast cancer patients before and after chemotherapy were compared to those of a local healthy control group, a local disease control group, and published norms, respectively, in order to determine whether the nature of the control group influenced outcome. The frequency of decline in the chemotherapy group was 21% and significantly higher than that of the control group whether referenced to the healthy controls, disease controls, or published norms. These results suggest that published norms may be adequate to demonstrate cancer-related cognitive impairment provided that cognitive function is measured adequately, practice effects and base rates are taken into account, and demographic factors that might influence practice effects are considered.

A pilot study of prospective memory functioning in early breast cancer survivors

AIMS To evaluate prospective memory (PM) functioning in early breast cancer (BC) survivors and its association with fatigue and depression. METHODS The Memory for Intention Screening Test, the Center for Epidemiologic Studies Depression Scale and the Functional Assessment of Cancer Therapy-Fatigue subscale were administered to 80 patients and 80 aged-matched healthy controls. RESULTS Patients performed more poorly than controls on the memory test (p < 0.001) and had a higher rate of impairment (odds ratio = 5.5, p < 0.01). Fatigue mediated the relationship between Group membership and PM performance. CONCLUSIONS BC survivors exhibited a clear pattern of PM deficit and fatigue was a major contributor to this deficit. This suggests that a common mechanism may be involved in fatigue symptoms and memory disturbances experienced by patients. Further research is needed to evaluate the role of adjuvant therapy in PM deficits and to explore whether interventions targeted at improving fatigue may also improve memory functioning in BC survivors.

Prospective memory impairment in chemotherapy-exposed early breast cancer survivors: Preliminary evidence from a clinical test

ABSTRACT We report the results of a secondary analysis of a cross-sectional study (Paquet et al., 2013) to evaluate the cognitive operations involved in prospective memory (PM) deficits exhibited by chemotherapy-exposed breast cancer (BC) survivors. PM was assessed with the memory for intentions screening test administered to 80 patients and 80 healthy controls. Patients performed worse than controls on the PM tasks and had more “omission” errors (indices of the prospective component of the tasks) than the controls. No group differences emerged on a recognition test. Although further studies will be needed to disentangle the multiple cognitive operations involved in PM, these findings are consistent with the notion that self-initiated retrieval processes rather than encoding are implicated in PM impairment among BC survivors.

Cancer-related cognitive impairment in breast cancer survivors: an examination of conceptual and statistical cognitive domains using principal component analysis

There is a great deal of variability in the composition of neuropsychological test batteries used in the assessment of cancerrelated cognitive impairment (CRCI). Not only the development of a gold standard approach for CRCI assessment would allow for easier identification of women suffering from CRCI but it would also promote optimal care for survivors. As a first step towards the development of a valid and reliable unified test battery, the objective of this study was to verify whether the theoretical domains commonly used in CRCI assessment are statistically supported, before and after breast cancer treatment. Principal component analyses (PCA) were performed on the results from 23 neuropsychological tests grouped into eight conceptual domains. For baseline data, the Kaiser-Meyer-Olkin was .82 and Bartlett’s X2(253, N=95) = 949.48, P<0.001. A five-component solution explained 60.94% of the common variance. For the post-treatment data, the Kaiser-Meyer-Olkin was .83 and Bartlett’s X2(253, N=95) = 1007.21, P<0.001 and a five component solution explained 62.03% of the common variance. Although a visual comparison of the theoretical model with those determined via PCA indicated important overlap between conceptual domains and statistical components, significant dissimilarities were also observed.