Cognitive function following breast cancer treatment and associations with concurrent symptoms.
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ABSTRACT:
SUBMITTER: Van Dyk K
PROVIDER: S-EPMC6098124 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Cognitive function following breast cancer treatment and associations with concurrent symptoms.
Van Dyk Kathleen K Bower Julienne E JE Crespi Catherine M CM Petersen Laura L Ganz Patricia A PA
NPJ breast cancer 20180817
Cognitive changes after breast cancer treatment are often attributed to chemotherapy, without considering other important factors such as other treatments (e.g., surgery, radiation, endocrine therapy (ET)). We compared neuropsychological functioning in the domains of learning, memory, attention, visuospatial, executive function, and processing speed according to primary breast cancer treatment exposures in early survivorship, before the initiation of ET (<i>n</i> = 189). We were also interested ...[more]
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Project description:BackgroundCancer-related fatigue, mood disturbances, pain and cognitive disturbance are common after adjuvant cancer therapy, but vary considerably between individuals despite common disease features and treatment exposures. A genetic basis for this variability was explored in a prospective cohort.MethodsPhysical and psychological health of women were assessed prospectively following therapy for early stage breast cancer with self-report questionnaires. Participation in a genetic association sub-study was offered. Indices for the key symptom domains of fatigue, pain, depression, anxiety, and neurocognitive difficulties were empirically derived by principal components analysis from end-treatment questionnaires, and then applied longitudinally. Genetic associations were sought with functional single nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes - tumour necrosis factor (TNF)-α (-308 GG), interferon (IFN)-ɣ (+874 TA), interleukin (IL)-10 (1082 GA and -592 CA), IL-6 (-174 GC), IL-1β (-511 GA).ResultsQuestionnaire data was available for 210 participants, of whom 111 participated in the genetic sub-study. As expected, symptom domain scores generally improved over several months following treatment completion. Tumour and adjuvant treatment related factors were unassociated with either severity or duration of the individual symptom domains, but severity of symptoms at end-treatment was strongly associated with duration for each domain (all p < 0.05). In multivariable analyses, risk genotypes were independently associated with: fatigue with IL-6 -174 GG/GC and IL-10 -1082 GG; depression and anxiety with IL-10 -1082 AA; neurocognitive disturbance: TNF-α -308 GG; depression IL-1β (all p < 0.05). The identified SNPs also had cumulative effects in prolonging the time to recovery from the associated symptom domain.ConclusionsGenetic factors contribute to the severity and duration of common symptom domains after cancer therapy.
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Project description:Behavioral symptoms are common in breast cancer survivors, including disturbances in energy, sleep, and mood, though few risk factors for these negative outcomes have been identified. Our study examined intrusive thoughts as a predictor of lingering symptoms in breast cancer survivors in the year following treatment.Data come from the Moving Beyond Cancer psychoeducational intervention trial, aimed at easing the transition from patient to survivor. Women (n = 558) completed psychosocial questionnaires within 4 weeks posttreatment and again 2, 6, and 12 months later. We examined intrusive thoughts about cancer at the baseline assessment as a predictor of fatigue, sleep problems, pain, breast cancer-specific symptoms, depressive symptoms, negative affect, and quality of life using growth curve modeling, controlling for study condition and other covariates.Intrusive thoughts were associated with higher levels of all symptoms at baseline and at the 12-month assessment. Intrusive thoughts also influenced the trajectory of pain, depressive symptoms, negative affect, and physical functioning over time; women with higher intrusions at baseline started worse and improved over time, whereas those with lower intrusions remained at a constant, lower level over time. Intrusions were not associated with the trajectory of fatigue, sleep, breast cancer-specific symptoms, or mental functioning; women with higher intrusions at baseline started worse and remained worse over time.Intrusive thoughts are associated with enduring elevations in behavioral symptoms and impaired quality of life in the year after breast cancer treatment and may be a risk factor for poor outcomes.
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Project description:BACKGROUND:Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare. METHODS:We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-?, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates. RESULTS:Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=-0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=-0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=-0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018). CONCLUSION:This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI.
| S-EPMC5768199 | biostudies-literature
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Project description:Treatment for breast cancer may result in the formation of palpable cords in the axillary region. Our aim was to evaluate cording incidence, risk factors, and association with upper extremity functional impairment and measured arm volume change. We included 308 patients with unilateral breast cancer prospectively screened for upper extremity lymphedema, symptoms and function. Patients were assessed pre- and post-operatively and at 3-8-month intervals with perometer arm measurements and the LEFT-BC questionnaire. Cording was determined by patient self-report. The cumulative incidence of cording and its association with clinicopathologic factors, upper extremity functional impairment, and measured arm volume change were analyzed. 31.5 % (97/308) of patients reported cording, with a cumulative incidence of 36.2 % at 24 months post-operative. Clinicopathologic factors significantly associated with cording by multivariate analysis included axillary lymph node dissection (p < 0.0001) and younger age at diagnosis (p = 0.0005). Cording was associated with increased functional impairment (p = 0.0018) and an arm volume increase of ?5 % (p = 0.028). Cording following breast cancer treatment is common, and may occur beyond the post-operative period. Our findings emphasize the importance of identifying patients at high risk for cording, and developing strategies to minimize functional impairment and arm volume elevation associated with cording. Future studies should investigate the effectiveness of interventions for cording following breast cancer treatment.
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Project description:BackgroundHot flushes and night sweats (HFNS) affect 65-85% of women after breast cancer treatment; they are distressing, causing sleep problems and decreased quality of life. Hormone replacement therapy is often either undesirable or contraindicated. Safe, effective non-hormonal treatments are needed. We investigated whether cognitive behavioural therapy (CBT) can help breast cancer survivors to effectively manage HFNS.MethodsIn this randomised controlled trial, we recruited women from breast clinics in London, UK, who had problematic HFNS (minimum ten problematic episodes a week) after breast-cancer treatment. Participants were randomly allocated to receive either usual care or usual care plus group CBT (1:1). Randomisation was done in blocks of 12-20 participants, stratifying by age (younger than 50 years, 50 years or older), and was done with a computer-generated sequence. The trial statistician and researchers collecting outcome measures were masked to group allocation. Group CBT comprised one 90 min session a week for 6 weeks, and included psycho-education, paced breathing, and cognitive and behavioural strategies to manage HFNS. Assessments were done at baseline, 9 weeks, and 26 weeks after randomisation. The primary outcome was the adjusted mean difference in HFNS problem rating (1-10) between CBT and usual care groups at 9 weeks after randomisation. Analysis of the primary endpoint was done by modified intention to treat. The trial is registered, ISRCTN13771934, and was closed March 15, 2011.FindingsBetween May 5, 2009, and Aug 27, 2010, 96 women were randomly allocated to group CBT (n=47) or usual care (n=49). Group CBT significantly reduced HFNS problem rating at 9 weeks after randomisation compared with usual care (mean difference -1·67, 95% CI -2·43 to -0·91; p<0·0001) and improvements were maintained at 26 weeks (mean difference -1·76, -2·54 to -0·99; p<0·0001). We recorded no CBT-related adverse events.InterpretationGroup CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood, sleep, and quality of life. The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses.FundingCancer Research UK.
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Project description:The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC).The participants were newly diagnosed EBC patients aged ?65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index.Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05).This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel.This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.
| S-EPMC5189619 | biostudies-literature
Project description:BackgroundSurvival 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.MethodsTo 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].ResultsVariables 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).ConclusionsWe 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.
| S-EPMC7716505 | biostudies-literature
Project description:CONTEXT:Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. OBJECTIVES:The objectives of this study were to identify prototypical presystemic therapy psychoneurological symptom clusters among older breast cancer survivors and determine whether these symptom clusters predicted cognition and QOL over time. METHODS:Women with newly diagnosed nonmetastatic breast cancer (n = 319) and matched noncancer controls (n = 347) aged 60+ years completed questionnaires and neuropsychological tests before systemic therapy and 12 and 24 months later. Latent class analysis identified clusters of survivors based on their pretherapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (Instrumental Activities of Daily Living disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. RESULTS:Nearly one-fifth of older survivors were classified as having high pretherapy symptoms (n = 51; 16%); the remainder had low symptoms (n = 268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24 months, lower functional well-being at baseline and 12 months, greater Instrumental Activities of Daily Living disability at baseline, and lower breast cancer-specific QOL at all time points (all P < 0.05). CONCLUSION:Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which predicted clinically meaningful decrements in perceived cognition and function in the first 24 months after diagnosis. Pretreatment psychoneurological symptom clusters could identify survivors for monitoring or intervention.
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