Cognitive impairment associated with chemotherapy for breast cancer: An exploratory case-control study

8501 Background: There is evidence that some women suffer cognitive impairment after adjuvant chemotherapy (CT) for breast cancer and it may be sustained. We report a case-control study to explore underlying mechanisms with blood tests and functional imaging. Methods: Women diagnosed with breast cancer within 5 years were recruited to 3 groups of 20. Cases (group A) had received CT and self-reported cognitive dysfunction on a prototype FACT-COG questionnaire. There were 2 groups of controls: group B had received CT but did not report cognitive problems; group C had breast cancer but did not receive CT. Comprehensive tests of cognitive function (2.5 hr) were performed. Blood tests evaluated sex hormones, coagulation factors, 10 cytokines, and apolipoprotein genotype. Functional MRI (fMRI) scans were performed while subjects performed a mental task. Results: Currently, 60 women have completed FACT-COG, 39 have undergone neuropsychological assessment and 31 have completed fMRI; testing and analysis will be complete by May 2006. Median time from diagnosis was 2 years. There was increased self-report of cognitive impairment in CT vs non-CT patients (p<0.0001). Formal cognitive testing disclosed more impairment in group C (no CT) as compared to groups A and B: 29% vs 0% by classical tests (p=0.046), and 61% vs 47% and 25% (p=0.38) by computerized testing. This may be due to slight imbalance of demographic factors. Decreased activation in fMRI was seen in frontal areas and right parahippocampus of women who self-reported greater cognitive impairment (p<0.0005), while separate frontal areas show increased activity in women with greater objective cognitive impairment (p<0.0005). Patients who received CT reported more fatigue than non-CT patients (p=0.027). There was an association between fatigue and self-reported cognitive impairment (p=0.004) and anxiety and depression (General Health Questionnaire) (p=0.009), but not with objective cognitive testing. As yet there is no significant correlation between symptoms and cytokine levels. Conclusions: Self-reported cognitive impairment is associated with prior chemotherapy and changes in fMRI but not with formal cognitive testing. The larger sample size is required to confirm these changes and explore possible mechanisms. No significant financial relationships to disclose.