A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer

Cancer Research UK Psychosocial Oncology Group, Brighton and Sussex Medical School, University of Sussex, East Sussex BN1 9QG, UK.
British Journal of Cancer (Impact Factor: 4.82). 04/2006; 94(6):828-34. DOI: 10.1038/sj.bjc.6603029
Source: PubMed

ABSTRACT The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

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Available from: Valerie Shilling, Jul 31, 2015
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    • "Particularly after adjuvant chemotherapy (CT), BC patients frequently report cognitive problems (Poppelreuter et al., 2004; Pullens, De Vries, & Roukema, 2010). Cognitive decline relative to pre-treatment cognitive functioning (Ahles et al., 2010; Jansen, Cooper, Dodd, & Miaskowski, 2011; Jenkins et al., 2006) was observed in numerous prospective studies, and several studies report cognitive impairment up to 20 years after treatment (Collins, Mackenzie, Tasca, Scherling, & Smith, 2013; de Ruiter et al., 2011; Koppelmans, Breteler, et al., 2012; Vearncombe et al., 2009; Wefel, Saleeba, Buzdar, & Meyers, 2010). The incidence of cognitive problems following chemotherapy varies considerably with estimates ranging from 20 to 70% (Wefel & Schagen, 2012). "
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    ABSTRACT: 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
    Journal of the International Neuropsychological Society 12/2014; 21(01). DOI:10.1017/S1355617714001015 · 3.01 Impact Factor
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    • "Despite the link between anxiety, depression and lower cognitive performance, evidence in the cancer/chemotherapy literature remains controversial . Some studies have found that high anxiety and depression scores are associated with lower performance in verbal memory and executive function tests (Ando-Tanabe et al. 2012) and overall cognitive function (Wefel et al. 2004), while others have found no association between the cognitive impairment experienced by cancer patients and levels of anxiety and/or depression (Hermelink et al. 2007; Jenkins et al. 2006; Collins et al. 2012). Fatigue is one commonly reported symptom experienced by both cancer patients and patients receiving chemotherapy (Spichiger et al. 2011; Mitchell 2010). "
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    ABSTRACT: Cognitive complaints by breast cancer survivors receiving chemotherapy have led to an increasing interest in elucidating the possible causes of such impairment. Although a number of neuroimaging studies have been conducted, only a handful of them have taken into account cognitive status pre-chemotherapy. The current study included pre-chemotherapy and post-chemotherapy assessment. In addition, various factors such as depression, anxiety, fatigue and days since surgery were considered during analyses. Breast cancer patients performed an fMRI verbal recall task before and an average of 1 month after chemotherapy. Well matched controls also performed the task with a similar timeline. Pre-chemotherapy analyses revealed that patients activated the anterior cingulate less than controls during memory retrieval when anxiety and fatigue scores were added as covariates during group comparisons. In addition, there were also changes in brain activation from pre- to post-chemotherapy in patients but not in controls. Post-chemotherapy, patients had less activation in the bilateral insula, the left inferior orbitofrontal cortex and the left middle temporal gyrus. Finally, patients also showed significantly less activation when compared to controls. Brain regions included: the right middle and superior temporal gyrus, the right medial frontal gyrus, the right inferior orbitofrontal cortex, the left insula and left superior temporal pole. Importantly, depression, anxiety, and particularly fatigue accounted for some of brain activation differences. Our results suggest that chemotherapy in part plays a role in brain activation differences and it also highlights the importance of rigorously controlling for confounding variables. Only by controlling such factors can we understand the role that chemotherapy may play on cognition.
    Brain Imaging and Behavior 12/2012; 7(4). DOI:10.1007/s11682-012-9213-0 · 4.60 Impact Factor
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    • "The course of cognitive complaints after cancer treatments is not known, as few long-term longitudinal studies have been conducted to date (Phillips et al., 2012; Jenkins et al., 2006; Syrjala et al., 2011). Animal studies also suggest the possibility of a biphasic pattern of injury with acute and then delayed toxicities (Han et al., 2008). "
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    ABSTRACT: Post-chemotherapy treated cancer patients frequently report cognitive difficulties. The biology of this phenomenon is poorly understood, with uncertainty about possible direct toxic effects on the brain, secondary effects from systemic inflammation, host factors/genetic predisposition to cognitive complaints, or hormonal changes influencing cognitive function. To elucidate possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors, in 2007 we established a prospective, longitudinal, observational cohort study of early stage breast cancer patients, recruited at the end of initial treatments (primary treatment exposure included surgery, ±radiation, ±chemotherapy), and prior to the initiation of adjuvant endocrine therapy. We assessed cognitive complaints, neuropsychological (NP) test performance, markers of inflammation, and brain imaging at baseline, 6months and 12months after enrollment. In this analysis of data from the first 93 patients enrolled in the cohort study, we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure. Among the proinflammatory cytokines tested (IL-1ra, sTNF-RII, CRP, and IL-6) at baseline, only sTNF-RII was increased among chemotherapy exposed patients, with a significant decline in the year after treatment (p=0.003). Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints. In chemotherapy exposed patients, the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12months (r=-0.34, p=0.04). Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex (r=-0.55, p=0.02), as well as relatively increased inferior frontal metabolism after 1year, in chemotherapy-exposed subjects. These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors.
    Brain Behavior and Immunity 08/2012; 30. DOI:10.1016/j.bbi.2012.07.015 · 6.13 Impact Factor
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