Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies.

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as "chemobrain", is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remain poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. Mediation analysis showed that the functional connectivity alteration pattern is a separable treatment symptom from the decreased cognitive health. Current study indicates that more targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health.

Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n = 28) or without (n = 34) chemotherapy for localized breast cancer and healthy controls (n = 30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre-adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post-baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors.

There is growing evidence that fluctuations in brain activity may exhibit scale-free (“fractal”) dynamics. Scale-free signals follow a spectral-power curve of the form P(f ) ∝ f−β, where spectral power decreases in a power-law fashion with increasing frequency. In this study, we demonstrated that fractal scaling of BOLD fMRI signal is consistently suppressed for different sources of cognitive effort. Decreases in the Hurst exponent (H), which quantifies scale-free signal, was related to three different sources of cognitive effort/task engagement: 1) task difficulty, 2) task novelty, and 3) aging effects. These results were consistently observed across multiple datasets and task paradigms. We also demonstrated that estimates of H are robust across a range of time-window sizes. H was also compared to alternative metrics of BOLD variability (SDBOLD) and global connectivity (Gconn), with effort-related decreases in H producing similar decreases in SDBOLD and Gconn. These results indicate a potential global brain phenomenon that unites research from different fields and indicates that fractal scaling may be a highly sensitive metric for indexing cognitive effort/task engagement.

Purpose/Objectives: To assess cognitive function in individuals with colorectal cancer (CRC) and identify factors associated with cognitive effects.Design: Cross-sectional, comparative design.Setting: Midwest hospital.Sample: Men and women with (n = 50) and without (n = 50) CRC.Methods: Comparative and regression analyses were performed to assess the relationship between cognition and CRC.Main Research Variables: Attention, cognitive control, and memory function were assessed with neuropsychological tests and self-report.Findings: Compared to healthy volunteers, individuals with CRC performed worse and reported more problems on tasks requiring attention and cognitive control (p < 0.05). After controlling for covariates, poorer performance on tasks of attention and cognitive control was associated (p < 0.001) with having CRC, older age, and less education. In contrast, poorer perceived attention and cognitive control were associated (p < 0.001) with greater fatigue but not CRC.Conclusions: Individuals with CRC are vulnerable to cognitive problems. In addition, older age, less education, and fatigue can increase risk for worse cognitive performance and self-reported cognition.Implications for Nursing: Cognitive problems can profoundly affect an individual's ability to function in everyday life and cope with cancer. Nurses should assess for cognitive problems in patients with CRC and intervene to reduce distress.

Stressful life events are related to negative outcomes, including physical and psychological manifestations of distress, and behavioral deficits. Patients diagnosed with breast cancer report impaired attention and working memory prior to adjuvant therapy, which may be induced by distress. In this article, we examine whether brain dynamics show systematic changes due to the distress associated with cancer diagnosis. We hypothesized that impaired working memory is associated with suppression of “long‐memory” neuronal dynamics; we tested this by measuring scale‐free (“fractal”) brain dynamics, quantified by the Hurst exponent (H). Fractal scaling refers to signals that do not occur at a specific time‐scale, possessing a spectral power curve P(f)∝f−β ; they are “long‐memory” processes, with significant autocorrelations. In a BOLD functional magnetic resonance imaging study, we scanned three groups during a working memory task: women scheduled to receive chemotherapy or radiotherapy and aged‐matched controls. Surprisingly, patients' BOLD signal exhibited greater H with increasing intensity of anticipated treatment. However, an analysis of H and functional connectivity against self‐reported measures of psychological distress (Worry, Anxiety, Depression) and physical distress (Fatigue, Sleep problems) revealed significant interactions. The modulation of (Worry, Anxiety) versus (Fatigue, Sleep Problems, Depression) showed the strongest effect, where higher worry and lower fatigue was related to reduced H in regions involved in visuospatial search, attention, and memory processing. This is also linked to decreased functional connectivity in these brain regions. Our results indicate that the distress associated with cancer diagnosis alters BOLD scaling, and H is a sensitive measure of the interaction between psychological versus physical distress. Hum Brain Mapp 36:1077–1092, 2015. © 2014 Wiley Periodicals, Inc.

Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short-and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.

Background: Cognitive deficits have been reported as detrimental side effects in chemotherapy-treated breast cancer patients and survivors. Korean women treated for breast cancer may experience unrecognized cognitive deficits related to their treatment. However, no research has examined cognitive test performance in chemotherapy-treated Korean breast cancer survivors. Objective: The objectives of this study were 2-fold: (1) to examine differences in occurrence and severity of cognitive deficits in Korean women treated with adjuvant chemotherapy for breast cancer as compared with a control group of women without breast cancer and (2) to examine the relationship of selected demographic and cultural factors with cognitive test performance. Methods: Sixty-four Korean women, 32 women treated for localized breast cancer and 32 healthy controls, were enrolled. Breast cancer participants were assessed with established cognitive measures within 4 months after chemotherapy, and healthy controls, within 6 months after negative screening mammography. Results: The breast cancer group showed a significantly higher occurrence and greater severity of cognitive deficits than controls did. Importantly, older age, less education, greater collectivist tendency, and greater childrearing burden were reliably associated with poorer attention and working memory test performance. Conclusions: Cognitive deficits were found in chemotherapy-treated Korean women with moderate to large effect sizes compared with controls. Cultural characteristics contributed to worse cognitive performance. Implications for Practice: Healthcare providers should recognize that Korean women may be highly vulnerable to cognitive deficits. Cultural factors also need to be considered when assessing cognitive function and designing therapeutic interventions to counteract negative cognitive outcomes.

UNLABELLED:[Correction Notice: An Erratum for this article was reported in Vol 33(3) of Health Psychology (see record 2014-07787-001). The name of author Misook Jung was misspelled as Mi Sook Jung. All versions of this article have been corrected.] OBJECTIVE:Altered cognitive function has been associated with breast cancer treatment, particularly adjuvant chemotherapy, but the underlying neuropsychological mechanisms are not yet understood. Recent research indicates that compromised attention and working memory can exist before adjuvant treatment, implicating psychological distress, such as worry, as a possible contributor to observed alterations in cognitive function. We hypothesized that worry associated with breast cancer diagnosis might influence neurocognitive responses before any adjuvant therapy. DESIGN:Fifty women, 25 due to receive chemotherapy and 25 due to receive radiation therapy, participated in the study. Women performed a verbal working memory task during functional magnetic resonance imaging scanning to assess neurocognitive responses before any adjuvant treatment and to test the relationship of such responses with self-reports of worry. RESULTS:Although prechemotherapy participants showed significantly higher levels of worry compared with preradiation participants, higher worry, across both groups, was related to altered brain function. Specifically, increased worry was associated with reduced demand-related deactivation in default-mode regions, such as the precuneus/posterior cingulate. Reduced demand-related deactivation was critically related to worse behavioral performance, which was partially mediated by worry. CONCLUSION:Worry appears to be a significant contributor to neurocognitive dysfunction independent of adjuvant treatment for breast cancer. These results suggest that alterations in cognitive function may develop before any chemotherapy treatment and that worry about cancer diagnosis may contribute to reports of "chemo brain" during treatment. Psychological interventions aimed at mitigating worry may help to alleviate cognitive dysfunction associated with life-threatening illness such as breast cancer.

Altered cognitive function can be a distressing side effect of cancer and its treatment. Women diagnosed and treated for breast cancer often report problems with memory, concentration, and other cognitive abilities that can pose significant barriers to full resumption of family, job, and social roles. Despite considerable neuropsychological research, many unanswered questions remain about cancer-related cognitive deficits and the underlying neural bases. Functional magnetic resonance imaging (fMRI) measures brain activation associated with different mental states and has significantly advanced our understanding of cognitive function and dysfunction in healthy and clinical populations. However, to date the application of fMRI to the study of cognitive function in breast cancer is limited. The current review addresses the potential importance of this method for understanding the neurocognitive effects of breast cancer disease and treatment. Along with reviewing published fMRI studies on breast cancer to date, we discuss potential major contributions of this method which include: (a) delineating components of cognitive function and underlying neural processes most affected by cancer and its treatment, (b) uncovering compensatory processes and their limits, (c) identifying altered resting state networks that may relate to subjective complaints and longer term outcomes, and (d) clarifying the relationship between pre-treatment alterations in brain activity and longer term neural and behavioral outcomes. Finally, we pose questions for future research that can be optimally addressed by integrating fMRI and other imaging modalities to clarify the nature and causes of “chemo brain” and guide interventions to improve cognitive function and the quality of breast cancer survivorship.

Cognitive effects of breast cancer therapies: univariate and multivariate analyses of brain connectivity Scott James Peltier, Marc Berman, Mary Kathleen Askren, Bratislav Misic, Mi Sook Jung, Anthony Randal McIntosh, Lynn Ossher, Min Zhang, Patricia ReuterLorenz, and Bernadine Cimprich University of Michigan, Ann Arbor, MI, United States, University of South Carolina, SC, United States, University of Washington, WA, United States, University of Toronto, Ontario, Canada

Women diagnosed with and treated for breast cancer often experience problems with memory, concentration, and other cognitive abilities that affect their quality of life [Reuter-Lorenz PA, Cimprich B. Breast Cancer Res Treat 2013]. Women treated for breast cancer often report fatigue, but an association between fatigue and neurocognitive function has not been systematically examined. This article presents data from a prospective functional MRI (fMRI) study on the neurocognitive impact of breast cancer-linked fatigue.

Objective: Cancer patients and partners often report inadequate communication about illness-related issues, although it is essential for mutual support and informal caregiving. This study examined the patterns of change in dyadic communication between patients with prostate cancer and their partners, and also determined if certain factors affected their communication over time.Objective: Cancer patients and partners often report inadequate communication about ill-nessrelated issues, although it is essential for mutual support and informal caregiving. This study examined the patterns of change in dyadic communication between patients with prostate cancer and their partners, and also determined if certain factors affected their communication over time.Method: Using multilevel modeling, this study analyzed longitudinal data obtained from a randomized clinical trial with prostate cancer patients and their partners, to examine their communication over time. Patients and partners (N=134 pairs) from the usual-care control group independently completed baseline demographic assessment and measures of social support, uncertainty, symptom distress, and dyadic communication at baseline, and 4-, 8-, and 12-month follow-ups.Results: The results indicated that (1) patients and partners reported similar levels of open communication at the time of diagnosis. Communication reported by patients and partners decreased over time in a similar trend, regardless of phase of illness; (2) phase of illness affected couples' open communication at diagnosis but not patterns of change over time; and (3) couples' perceived communication increased as they reported more social support, less uncertainty, and fewer hormonal symptoms in patients. Couples' demographic factors and general symptoms, and patients' prostate cancer-specific symptoms did not affect their levels of open communication.Conclusions: Perceived open communication between prostate cancer patients and partners over time is affected by certain baseline and time-varying psychosocial and cancer-related factors. The results provide empirical evidence that may guide the development of strategies to facilitate couples' interaction and mutual support during survivorship. Copyright (C) 2010 John Wiley & Sons, Ltd.

Abstract Background: Our previous research showed evidence of compromised cognitive function prior to adjuvant chemotherapy for breast cancer, with fatigue as a contributory factor. Fatigue is a common symptom reported by women treated for breast cancer, yet its association with neurocognitive function has not been systematically examined. In this prospective study, we examined possible alterations in neurocognitive responses, namely, working memory, from pre- to post- adjuvant treatment during functional magnetic resonance imaging (fMRI) and further investigated whether early fatigue might be linked to cognitive alterations over time. Methods: Women treated with either adjuvant chemotherapy (anthracyline-based combination regimen, n=29) or radiotherapy (n = 37) for localized breast cancer (Stages 0-IIIa) and age-matched healthy controls (n = 32) were enrolled. Participants performed a verbal working memory task (VWMT) with varying levels of demand for cognitive control during fMRI scanning and provided self-reports of fatigue (FACT-F) at two time points coincident with pre- and one-month post chemotherapy assessments. Imaging data were analyzed with general linear models using SPM5; comparative statistics were used to determine group differences, and correlational analyses addressed relationships of fatigue and neurocognitive measures. Findings: The chemotherapy group reported significantly greater severity of fatigue (p < .05) and performed less accurately on the VWMT both pre- and one-month post-treatment than the other groups. Greater fatigue was correlated with poorer performance on the VWMT at both time points across groups, with stronger correlation post-treatment (r = −.22, p = .03). A 2 time-point (pre- vs. post-treatment) × 2 group (chemotherapy vs. controls) × 2 demand-level contrasts (high minus low vs. medium minus low) analytic model showed a significant group × time interaction (p < .05), mainly due to lower pre-treatment activation in an area of the prefrontal cortex supporting working memory, the anatomical left inferior frontal gyrus (LiFG), at higher task demand in the chemotherapy group. The radiotherapy group scored between the other two groups with intermediate activation of those contrasts. Of interest, lower pre-treatment activation in the LiFG in the high-low demand contrast predicted severity of fatigue across all participants at the post-treatment assessment (r = −.27, p < .01), linking early compromise in neurocognitive performance with greater fatigue over time. Discussion: Neurocognitive alterations during a working memory task and greater fatigue were evident before any adjuvant chemotherapy for breast cancer. Notably, functional alterations in working memory processes were evident with fMRI before adjuvant chemotherapy and predicted severity of post-treatment fatigue. Importantly, across all participants, greater fatigue over time was correlated with reduced cognitive performance. Taken together, these findings indicate that pre-treatment neurocognitive compromise and fatigue are key contributors to the cognitive impact often attributed solely to chemotherapy. Early therapeutic interventions targeting fatigue may improve cognitive function and reduce the distress of “chemo brain” throughout the course of adjuvant treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S6-3.

Objective: Cognitive assessment in individuals with cancer requires both measured performance on neuropsychological tests and self-report of effectiveness in functioning. Few instruments are available to assess the perceived impact of cognitive alterations on daily functioning in individuals treated for cancer. In this study, we investigated the psychometric properties of a theoretically based instrument, and the Attentional Function Index (AFI), designed to measure perceived effectiveness in common activities requiring attention and working memory, particularly the ability to formulate plans, carry out tasks, and function effectively in daily life.Methods: Women (N = 172), ages 27-86 years, completed the questionnaire before primary treatment for early stage breast cancer. Construct validity was established using exploratory principal component factor analysis with varimax rotation.Results: A 13-item instrument emerged with 3 subscales, namely effective action, attentional lapses, and interpersonal effectiveness, which explained 74.69% of total variance. The internal consistency coefficients (Cronbach's alpha) were 0.92 for the total instrument, and ranged from 0.80 to 0.92 for the 3 subscales. Further examination of validity indicated that the scores on the AFI (1) showed expected correlations with established measures of ability to concentrate, cognitive failures, states of confusion, and mental fatigue, and (2) could distinguish differences in perceived cognitive functioning between younger and older age groups. AFI scores were not significantly associated with years of education or presence of comorbid conditions.Conclusion: The brief AFI has demonstrated usefulness for assessment of perceived cognitive functioning in populations with life-threatening and chronic illness, such as breast cancer. Copyright (C) 2010 John Wiley & Sons, Ltd.

Purpose This study aimed at examining the relationship between quality of life (QOL) in prostate cancer (PCa) patients and partners and how baseline demographics, cancer-related factors, and time-varying psychosocial and symptom covariates affect their QOL over time. Methods Guided by a modified Stress-Coping Model, this study used multilevel modeling to analyze longitudinal data from a randomized clinical trial that tested a family-based intervention to improve QOL in couples managing PCa. Patients and partners from the usual-care control group ( N = 134 dyads) independently completed the measurements at baseline, and at 4-, 8-, and 12-month follow-ups. Results Correlations of QOL between patients and partners over time were small to moderate. Patients’ lower education level, partners’ older age, higher family income, and localized cancer at baseline were associated with better QOL in couples. Over time, couples’ QOL improved as their social support and cancer-related dyadic communication increased and as couples’ uncertainty, general symptoms, and patients’ prostate cancer-related sexual and hormonal symptoms decreased. Conclusions Evidence indicates that couples’ QOL during cancer survivorship is affected by multiple contextual factors (e.g., baseline demographics and time-varying psychosocial factors and symptoms). Intervention research is needed to explore comprehensive strategies to improve couples’ QOL during the continuum of PCa survivorship.

Abstract Background: The underlying brain mechanisms of altered cognitive function associated with adjuvant chemotherapy for breast cancer, commonly designated “chemobrain”, have yet to be determined. Recent research indicates that compromised cognitive function may already exist prior to treatment, adding to the complexity of determining the true impact of adjuvant chemotherapy on brain function. We examined whether two common symptoms associated with breast cancer diagnosis, worry and fatigue, might influence neurocognitive responses during functional magnetic resonance imaging (fMRI) before adjuvant therapy. Methods: Seventy five women (29–75 years) awaiting either adjuvant chemotherapy (n=25) or radiation therapy (n=25) for localized breast cancer and age-matched controls without breast cancer (n=25) were enrolled. Participants performed a verbal working memory task (VWMT) with varying levels of demand for cognitive control during fMRI scanning and provided self-reports of worry and fatigue after scanning. Imaging data were analyzed using the general linear model implemented in SPM5; comparative statistics were used to determine group differences in self-report and behavioral measures. Results: In general, the pre-chemotherapy group showed compromised cognitive functioning relative to the other groups. Specifically, they reported higher worry than the pre-radiation therapy (p=.036) and control (p=.047) groups. The pre-chemotherapy group also identified greater fatigue than controls (p=.04); the pre-radiation group reported a fatigue level between the other two groups. In the VWMT, the pre-chemotherapy group was less accurate than controls (p=.05), while the mean accuracy for the pre-radiation group again fell between these two groups. fMRI results showed that the control group selectively increased recruitment of executive control brain regions including the left inferior frontal gyrus (LIFG) and the anterior cingulate cortex (ACC) in response to high vs. low demand conditions. However, recruitment of LIGF and ACC by the control group was greater than that by both the pre-chemotherapy (p=.01 and p=.003 respectively) and the pre-radiation groups (p=.027 and p=.02 respectively). Overall, higher fatigue was correlated with failure to increase recruitment of the LIFG and ACC in high vs. low demand conditions (p=.002 and p=.078 respectively). Greater worry was correlated with failure to suppress task-irrelevant activation of default network regions, particularly the posterior cingulate cortex, in high vs. low demand conditions, and with lower accuracy in the VWMT (p=.01). Thus, fatigue and worry made independent contributions to altered neurocognitive responses prior to any adjuvant treatment. Discussion: These findings suggest that women awaiting adjuvant chemotherapy are vulnerable to compromised cognitive functioning, specifically in the domains of attention and working memory, related to higher worry and fatigue. Worry and fatigue may contribute to the cognitive impact often attributed to adjuvant chemotherapy. Therapeutic interventions to counteract worry and fatigue hold potential for optimizing cognitive function prior to adjuvant treatment for breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-08.