Abstract P4-19-03: A meta-analysis of cognitive impairment in breast cancer survivors treated with chemotherapy
Authors: Bernstein LJ , McCreath GA , Rich JB 
Published: March 2017

Abstract
Background: Cognitive impairment in women with breast cancer has long been attributed to chemotherapy, but the evidence for this has been inconsistent, and more recent research suggests that additional cancer- and treatment-related factors also impact cognition. To systematically evaluate and describe “chemobrain,” a multilevel meta-analysis of objective cognitive function in breast cancer survivors treated with chemotherapy was conducted to estimate the magnitude of impairment across 9 cognitive domains and explore moderating variables.
Method: PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and PsycINFO were searched from their inception to May 2016 to identify studies that compared the cognitive performance of survivors treated with chemotherapy to a control group or to their own prechemotherapy testing. Multilevel modelling was used to account for the interdependence among effect sizes obtained within the same study.
Results: Seventy-seven studies involving 3417 cancer patients treated with chemotherapy yielded 1548 effect sizes. Cross-sectional comparisons revealed worse overall cognitive performance in survivors treated with chemotherapy relative to healthy controls (d = -0.27, 95% CI [-0.32, -0.21]) but not disease-specific controls (d = -0.07, 95% CI [-0.14, 0.00]). Relative to all controls, cognitive impairment in survivors treated with chemotherapy was observed in tests assessing language (d = -0.25), executive function (d = -0.21), processing speed (d = -0.15), delayed recall (d = -0.15), and attention/concentration (d = -0.14), but not in visual/spatial perception, immediate recall, recognition memory, or psychomotor domains. Because patients and controls were not well matched in many studies on age, education, and IQ, which are known to impact cognitive test performance, group differences in these variables were explored as moderators of observed cognitive deficits in post hoc analyses. Results showed that chemotherapy patients and controls performed equivalently when the controls were 6 years older or had 1 less year of education. Longitudinal comparisons showed improved postchemotherapy performance relative to prechemotherapy baseline, but practice effects were not accounted for in these comparisons.
Conclusion: Breast cancer survivors treated with chemotherapy show subtle yet diffuse cognitive impairment. Their cognitive performance was equivalent to that of women in comparison groups who were 6 years older, which suggests that chemotherapy accelerates cognitive aging. Results from breast cancer patients who were not treated with chemotherapy, however, indicate that chemotherapy is not the only determinant of cognitive dysfunction. Group differences in age and education moderated the magnitude of cognitive impairment. The cognitive reserve framework, which posits that individuals differ in the degree of neural disruption they can withstand before exhibiting cognitive deficits, should be considered in future studies in order to better understand moderating effects on cancer-related cognitive dysfunction. In particular, both cross-sectional and longitudinal studies should ensure that comparison cohorts are closely matched on age, education, and other relevant cognitive reserve variables.
Citation Format: Bernstein LJ, McCreath GA, Rich JB. A meta-analysis of cognitive impairment in breast cancer survivors treated with chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-19-03.