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Purpose: Cognitive dysfunction in women with breast cancer continues to be an area of intense research interest. The prevalence, severity, timing, and cognitive domains that are most affected, as well as the contribution of cancer and its treatments to cognition, remain unresolved. Thus, longitudinal studies are needed that examine cognitive function during different stages of breast cancer treatment and survivorship. This longitudinal trial followed women with early-stage breast cancer, prior to chemotherapy through 2 years survivorship., Methods: In women with early-stage breast cancer (N = -75), performance-based assessment of nine cognitive domains was performed at five time points beginning prior to chemotherapy and finishing 24 months after initial chemotherapy. Linear mixed effects models were used to examine the temporal changes in cognitive performance domains, while adjusting for cofactors, including those related to individuals, tumor attributes, chemotherapy (adjuvant or neoadjuvant), radiation, endocrine therapy, and concurrent symptoms., Results: At baseline, scores on reaction time, complex attention, cognitive flexibility, executive function, and visual memory were lower than 90. At 2 years, all domains improved except for the memory domains (verbal, visual, and composite). Scores on six domains (psychomotor speed, reaction time, complex attention, cognitive flexibility, and visual memory) remained lower than 100 at 2 years. Neoadjuvant chemotherapy and fatigue had strong inverse relationship with cognitive functioning at multiple time points., Conclusion: The low performance-based cognitive scores at baseline and over time warrant further study. Although most scores improved over time, memory did not improve. In all, the level of cognitive function is lower than expected for a majority college-educated sample. Thus, future studies are warranted to replicate these findings and to develop methods for identifying women with cognitive dysfunction pretreatment and into survivorship.

Objective: Fatigue and cognitive dysfunction are major concerns for women with early-stage breast cancer during treatment and into survivorship. However, interrelationships of these phenomena and their temporal patterns over time are not well documented, thus limiting the strategies for symptom management interventions. In this study, changes in fatigue across treatment phases and the relationship among fatigue severity and its functional impact with objective cognitive performance were examined.Methods: Participants (N = 75) were assessed at five time points beginning prior to chemotherapy to 24 months after initial chemotherapy. Fatigue severity and impact were measured on the Brief Fatigue Inventory. Central nervous system (CNS) Vital Signs was used to measure performance based cognitive testing. Temporal changes in fatigue were examined, as well as the relationship between fatigue and cognitive performance, at each time point using linear mixed effect models.Results: Severity of fatigue varied as a function of phase of treatment. Fatigue severity and its functional impact were moderate at baseline, increased significantly during chemotherapy, and returned to near baseline levels by 2 years. At each time point, fatigue severity and impact were significantly associated with diminished processing speed and complex attention performance.Conclusions: A strong association between fatigue and objective cognitive performance suggests that they are likely functionally related. That cognitive deficits were evident at baseline, whereas fatigue was more chemotherapy dependent, implicates that two symptoms share some common bases but may differ in underlying mechanisms and severity over time. This knowledge provides a basis for introducing strategies for tailored symptom management that vary over time. [ABSTRACT FROM AUTHOR]

Background: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction.Methods: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay].Results: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores).Conclusions: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to explore clusters of psychoneurological symptoms and inflammation (levels of C-reactive protein) over time in a cohort of women with early-stage breast cancer. Specifically, we examined the relationships among affective symptoms (depression, anxiety, fatigue, sleep disturbances, pain, and perceived stress), domains of cognitive performance, and levels of peripheral C-reactive over a period of 2 years.Methods: This was a prospective, longitudinal study of 77 women diagnosed with early-stage breast cancer. Data collection, including symptom questionnaires, performance-based cognitive testing, and blood draws, took place at 5 time points: prior to initiating adjuvant chemotherapy, prior to the fourth chemotherapy treatment, and at 6, 12, and 24 months after the initiation of chemotherapy.Results: Exploratory factor analysis with varimax orthogonal rotation was used to examine the covariance among symptoms at each visit. Using the factor scores and weighted sums, three clusters were identified: global cognition, affective symptoms, and cognitive efficiency. Peripheral levels of C-reactive protein were inversely correlated with the cognitive efficiency factor across time.Conclusions: The findings suggest that objectively measured domains of cognitive function occur independently of other affective symptoms that are commonly reported by women with breast cancer in long-term survivorship. The cognitive efficiency symptom cluster may be amenable to interventions targeted to biological influences that reduce levels of C-reactive protein. [ABSTRACT FROM AUTHOR]

Cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). While CRCI has been associated with linked to chemotherapy, there is increasing evidence that the condition may start prior to treatment and for some, remain unresolved after active treatment and into survivorship. Although the pathophysiology of the condition is complex, alterations in systemic cytokines, signaling molecules activated in response to infection or injury that trigger inflammation, are a possible mechanism linked to cognitive dysfunction in breast cancer and other conditions. Given the conflicting results in the literature, the lack of focus on domain specific cognitive testing, and the need for a longer time period given the multiple modalities of standard treatments for early-stage breast cancer, this longitudinal study was conducted to address these gaps. Methods We assessed 75 women with early-stage breast cancer at five points over two years, starting prior to the initial chemotherapy through 24 months after chemotherapy initiation. Measures included a validated computerized evaluation of domain-specific cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations to each cognitive domain. Results Levels and patterns of cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12, IL-17, G-CSF, MIPS-1β, and MCP-1) had the most variability. Some cytokine levels (e.g., IL-6) increased during chemotherapy but then decreased subsequently, while others (e.g., IL-17) consistently declined from baseline over time. There were multiple relationships among cytokines and cognition, which varied over time. At baseline, elevated concentrations of G-CSF and reduced concentrations of IL-17 were associated with faster psychomotor speed. At the second time-point (prior to the mid-chemotherapy), multiple cytokines had significant associations with psychomotor speed, complex attention, executive function, verbal memory, cognitive flexibility, composite memory and visual memory. Six months after chemotherapy initiation and at the one-year point, there were multiple, significant relationships among cytokines and multiple cognitive. At two years, fewer significant relationships were noted; however, lower concentrations of IL-7, a hematopoietic cytokine, were associated with better psychomotor speed, complex attention, and memory (composite, verbal and visual). MCP-1 was inversely associated with psychomotor speed and complex attention and higher levels of MIP-1β were related to better complex attention. Conclusion Levels and patterns of cytokines changed over time and demonstrated associations with domain-specific cognitive functioning that varied over time. The observed associations between cytokines and cognitive performance provides evidence that not only prototypical cytokines (i.e., IL-6, TNF-α, and IL1-β) but also cytokines from multiple classes may contribute to the inflammatory environment that is associated with cognitive dysfunction. Future studies to better delineate the cytokine changes, both individually and in networks, are needed to precisely assess a mechanistic link between cytokines and cognitive function in women receiving treatments for breast cancer. [ABSTRACT FROM AUTHOR]