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    Research Grants Awarded

    Mechanisms of Cognitive Dysfunction in Breast Cancer Survivors

    Study Section:
    Psycho-Social and Complementary Treatment

    Scientific Abstract:
    Background: Most women who receive adjuvant chemotherapy for breast cancer have fatigue and some complain also of changes in memory, attention, and/or concentration. Despite various methodological problems, investigations have provided consistent evidence for cognitive impairment in a subset of patients. Objectives/Hypothesis: To evaluate mechanisms of fatigue and cognitive dysfunction associated with chemotherapy in breast cancer survivors. We hypothesize that fatigue and cognitive dysfunction are associated with circulating levels of inflammatory cytokines, that cognitive dysfnunction is associated with a hypercoagulable state leading to blood clotting in small vessels of the brain, and that chemotherapy may lead to changes in brain function that can be detected by MRI. Specific Aims: (i) To evaluate cytokine levels and clotting factors from the multiple samples of frozen sera from 93 subjects (62 patients on and after chemotherapy, 31 controls) who participated in a prior study of fatigue and cognitive function. (ii) To expand a case-control study of cognitive dysfunction related to chemotherapy that was initiated with a pilot grant. Study Design: Cognitive function, assessed by the High Sensitivity Cognitive Screen, and levels of fatigue, evaluated by the FACT-F are known for all subjects who donated sera. Associations will be sought between levels of fatigue and cognitive dysfunction with serum tests. In the case control study, group A (“cases”) are breast cancer survivors within 5 years of adjuvant chemotherapy who indicate cognitive changes on a self-report questionnaire (prototype FACT-COG), group B are similarly treated “controls” who report no such impairment, and group C are breast cancer survivors who did not receive chemotherapy. All subjects undergo in-depth neuropsychological assessment with added tests of multitasking and everyday activity, donate blood which is analyzed for above factors, and undergo MRI of the head while performing cognitive tasks. Potential Outcomes and Benefits: Fatigue and cognitive dysfunction are recognized by breast cancer survivors as important side-effects of treatment that impair function and quality of life. Here we propose to study putative mechanisms that will facilitate the rational design of intervention studies Our long-term goal is to improve the ability of breast cancer survivors to function in their day-to-day activity, and thereby to improve their quality of life.

    Lay Abstract:
    Background: Most women who receive adjuvant chemotherapy become tired, and fatigue improves slowly. Some women also complain that their memory, attention, and/or concentration are less sharp than prior to diagnosis, and studies have provided evidence for subtle cognitive impairment. Both fatigue, and cognitive problems (referred to often as “chemobrain”), can disturb the return to a normal home and work life of cancer survivors. Objectives/Hypothesis: To study the causes of fatigue and cognitive problems that are associated with chemotherapy in breast cancer survivors. We hypothesize that these symptoms are associated with (a) increased levels of molecules called cytokines, and/or (b) blood clotting in small vessels of the brain leading to secondary damage. We also propose that women with cognitive problems will have changes in brain function that can be detected when undertaking a simple problem while having an MRI scan of the head. Specific Aims: (i) To measure levels of cytokines, and of factors associated with blood clotting from multiple blood samples that we have stored frozen from 93 subjects (62 patients on or after chemotherapy, 31 women without cancer) who took part in a prior study. (ii) To expand a study comparing breast cancer survivors with and without cognitive problems related to chemotherapy that was initiated with a pilot grant. Study Design: Levels of fatigue and of cognitive function were evaluated for all subjects at the times that they donated blood. We will seek associations between fatigue and cognitive problems with the results of the blood tests. We will also compare breast cancer survivors within 5 years of receiving chemotherapy who report cognitive problems, similarly treated women who report no such problems, and breast cancer survivors who did not receive chemotherapy. All subjects undergo in-depth assessment of their cognitive function, with added tests of multiple tasking and everyday activity, that appear to be affected in women who report problems. They also donate blood which is analyzed as described above, and undergo an MRI scan of the head while performing a simple mental task. Potential Outcomes and Benefits: Fatigue and cognitive problems are recognized by breast cancer survivors as important side-effects of treatment that can impair their function and quality of life. Here we plan to study possible causes that should allow the rational design of strategies to prevent or minimize these problems.