Although adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on cognition and brain function, studies on adverse effects of specific treatment regimens are scarce. Here, neurotoxicity profiles after different treatment strategies were compared in BC survivors randomized to high-dose (HI) or conventional-dose (CON-) CT, in women treated with radiotherapy (RT) -only and a healthy control (HC) group. We administered a neurocognitive test battery, a planning fMRI task (Tower of London) and episodic memory fMRI task (Paired Associates paradigm) in BC survivors who received CON-CT (n=24) and HC (n=27). Data were compared to BC survivors who received HI-CT (n=17) and RT-only (n=15) and who were previously assessed. Testing took place ±11.5 years post-CT. Furthermore, neurocognitive data were compared to neurocognitive data acquired ≤2 years post-treatment. Cognitive assessment revealed sustained cognitive decline in 10.5% of HI-CT, 8.3% of CON-CT, 6.7% of RT-only patients and 0% in the HC. Hypoactivation was found in task-related prefrontal and parietal areas for both CT-groups versus RT-only, with HI-CT showing more pronounced hypoactivation than CON-CT, combined with worse task performance. RT-only survivors performed at a similar level to HC while showing hyperactivation in task-related brain areas. Long after treatment, CT is associated with cognitive problems and task-related hypoactivation that depend on the specific cytotoxic regimen. This worse performance in patients who received CT could be explained by impaired brain functioning that is more severe with more intense CT. (JINS, 2015, 21, 50–61)

The objective of this study is to identify whether decline in cognitive functioning after chemotherapy in women with breast cancer is associated with health/disease, treatment, and psychological variables. Neuropsychological performance, health/disease, and treatment-related information of 136 women with breast cancer (age M = 49.38; SD = 7.92; range = 25.25–67.92) was assessed pre-chemotherapy and 1-month post-chemotherapy. The Reliable Change Index corrected for practice (RCIp) identified women whose performance significantly declined, while Pearson correlations assessed the relationship between cognitive change and predictor variables. A total of 16.9% of women showed significant decline post-chemotherapy, with affected domains including verbal learning and memory, abstract reasoning, and motor coordination. Decline in hemoglobin levels and increased anxiety over the course of chemotherapy was found to significantly predict impairment in multiple cognitive measures. Change in specific cognitive measures was significantly associated with baseline fatigue, depression, and functional well-being (r = 0.23 to 0.33; p = .01 to < .001). Although the effects are small, there is evidence that psychological and health factors may increase vulnerability to cognitive dysfunction after chemotherapy for breast cancer. Significant associations reported in this study may be useful in the identification and treatment of at-risk individuals. (JINS, 2009, 15, 951–962.)