Preventing Sleep Disruption With Bright Light Therapy During Chemotherapy for Breast Cancer: A Phase II Randomized Controlled Trial.

Purpose: The goal of this study was to examine whether daily increased morning light exposure would maintain or improve sleep and the circadian pattern of relatively more activity in the day and less during the night in women undergoing chemotherapy for breast cancer. Patients and Methods: Participants were 39 women with newly diagnosed breast cancer, randomized to either 30-mins of daily morning bright white light (BWL) or dim red light (DRL). Sleep/wake was measured objectively for 72-h with wrist actigraphy and subjectively with the Pittsburgh Sleep Quality Index (PSQI) prior to and during chemotherapy cycles 1 and 4. The study was registered with the National Institutes of Health ClinicalTrials.gov (Clinical Trials number: NCT00478257). Results: Results from actigraphy suggested that compared to the DRL group, women in the BWL group had longer night-time sleep, fewer sleep disturbances during the night, and had fewer and shorter daytime naps at the end of cycle 4 of chemotherapy as well as exhibiting less activity at night and more activity during the day by the end of cycle 4. Results from PSQI indicated that components of sleep quality improved but daytime dysfunction deteriorated during cycle 4 treatment in the BWL group; meanwhile the DRL group used more sleep medications in the treatment weeks which might have led to the improved sleep quality during the recovery weeks of both cycles. Conclusion: These results suggest that bright white light therapy administered every morning on awakening may protect women undergoing chemotherapy for breast cancer from nighttime sleep and daytime wake disruption. Randomized clinical trials in larger samples are needed to confirm these findings.

Reductions in sleep quality and circadian activity rhythmicity predict longitudinal changes in objective and subjective cognitive functioning in women treated for breast cancer.

PURPOSE: To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC). PATIENTS AND METHODS: Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year). RESULTS: WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood. CONCLUSION: Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

Circadian Contrasts in Heart Rate Variability Associated With Posttraumatic Stress Disorder Symptoms in a Young Adult Cohort.

Prior research has demonstrated that individuals exposed to trauma have shown impaired autonomic function. We sought to determine if heart rate variability (HRV), a marker of impaired autonomic function, differed across periods of wake, rest, and sleep as a function of the level of symptoms of posttraumatic stress disorder (PTSD). A sample of young adults (N = 209), 95 of whom met full criteria for current PTSD based on the Clinician Administered PTSD Scale (CAPS; Blake et al., 1995), were evaluated for ≈ 24 hr using actigraphy and electrocardiogram. Actigraphy data were categorized as active, rest, or sleep. Multilevel modeling analyses showed that individuals with high PTSD symptom severity had lower high-frequency HRV than individuals with low PTSD symptom severity during periods of sleep, t(1083) = 2.20, p = .028, Cohen's d = 0.12. No differences were found during periods of activity, t(1083) = 1.34, p = .499, d = 0.05, or rest, t(1083) = 1.34, p = .180, d = 0.09. Our findings extended the import of prior studies to suggest that those with elevated PTSD symptoms may have decreased parasympathetic control during sleep. Moreover, relative to periods of wake and rest, sleep may represent a state of increased vulnerability for decreased parasympathetic cardiac control. Individuals with elevated PTSD symptoms may benefit from early screening for detection of cardiovascular disease.

Aberrant nocturnal cortisol and disease progression in women with breast cancer.

While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

Sleep Disturbance, Diabetes, and Cardiovascular Disease in Postmenopausal Veteran Women.

PURPOSE OF THE STUDY: To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI). DESIGN AND METHODS: The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans. RESULTS: Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans. IMPLICATIONS: Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.

Pre-diagnostic Sleep Duration and Sleep Quality in Relation to Subsequent Cancer Survival.

STUDY OBJECTIVES: Poor sleep quality and short sleep duration have been associated with elevated risk for several cancer types; however, the relationship between sleep and cancer outcomes has not been well characterized. We assessed the association between pre-diagnostic sleep attributes and subsequent cancer survival within the Women's Health Initiative (WHI). METHODS: We identified WHI participants in whom a first primary invasive cancer had been diagnosed during follow-up (n = 21,230). Participants provided information on sleep characteristics at enrollment. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between these pre-diagnostic sleep characteristics and cancer-specific survival for all cancers combined and separately for common cancers. Analyses were adjusted for age, study arm, cancer site, marital status, income, smoking, physical activity, and time to diagnosis. RESULTS: No individual pre-diagnostic sleep characteristics were found to be significantly associated with cancer survival in analyses of all cancer sites combined; however, women who reported short sleep duration (≤ 6 h sleep/night) combined with frequent snoring (≥ 5 nights/w experienced significantly poorer cancer-specific survival than those who reported 7-8 h of sleep/night and no snoring (HR = 1.32, 95% CI: 1.14-1.54). Short sleep duration (HR = 1.46, 95% CI: 1.07-1.99) and frequent snoring (HR = 1.34, 95% CI: 0.98-1.85) were each associated with poorer breast cancer survival; those reporting short sleep combined with frequent snoring combined had substantially poorer breast cancer survival than those reporting neither (HR = 2.14, 95% CI: 1.47-3.13). CONCLUSIONS: Short sleep duration combined with frequent snoring reported prior to cancer diagnosis may influence subsequent cancer survival, particularly breast cancer survival.

Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study.

PURPOSE OF THE STUDY: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI). DESIGN AND METHODS: We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. RESULTS: Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). IMPLICATIONS: Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.

The Relationship Between Posttraumatic Stress Symptoms and Physical Health in a Survey of U.S. Veterans of the Iraq and Afghanistan Era.

BACKGROUND: Although a large body of literature has linked posttraumatic stress disorder (PTSD) with poor physical health among older veterans, less is known regarding the association between PTSD and health among relatively younger cohorts of veterans. OBJECTIVE: The current study examined the association between PTSD and self-reported health among a sample of veterans who served in the recent conflicts in Iraq and Afghanistan. METHOD: Veterans (N = 1030) who served in the wars in Iraq and Afghanistan completed measures of PTSD symptom severity and self-rated health between September 2009 and February 2010. Analyses examined the association between PTSD symptoms and health outcomes. RESULTS: In analyses adjusted for age, sex, race, and combat exposure, PTSD symptom severity was positively related to the number of health conditions and health symptoms reported (ps<0.001). Additionally, in analyses adjusted for age, sex, race, combat exposure, number of health conditions, and number of health symptoms, PTSD symptom severity was associated with an increased likelihood of rating one's health as poor or fair and an increased likelihood of reporting that one's physical health limits participation in activities (ps<0.001). CONCLUSION: These findings suggest that, consistent with previous research, PTSD symptom severity has a broad negative effect on physical health among veterans of the Iraq and Afghanistan era. Health promotion among veterans with PTSD may help attenuate risk of physical health consequences.

DSM-5 posttraumatic stress disorder: factor structure and rates of diagnosis.

Posttraumatic stress disorder (PTSD) is a significant problem among Iraq/Afghanistan-era veterans. To date, however, there has been only limited research on how the recent changes in DSM-5 influence the prevalence and factor structure of PTSD. To address this key issue, the present research used a modified version of a gold-standard clinical interview to assess PTSD among a large sample of Iraq/Afghanistan-era veterans (N = 414). Thirty-seven percent of the sample met DSM-5 criteria for PTSD compared to a rate of 38% when DSM-IV diagnostic criteria were used. Differences in rates of diagnosis between DSM-IV and DSM-5 were primarily attributable to changes to Criterion A and the separation of the "avoidance" and "numbing" symptoms into separate clusters. Confirmatory factor analysis (CFA) was used to compare the fit of the previous 3-factor DSM-IV model of PTSD to the 4-factor model specified in DSM-5, a 4-factor "dysphoria" model, and a 5-factor model. CFA demonstrated that the 5-factor model (re-experiencing, active avoidance, emotional numbing, dysphoric arousal, anxious arousal) provided the best overall fit to the data, although substantial support was also found for the 4-factor DSM-5 model. Low factor loadings were noted for two of the symptoms in the DSM-5 model (psychogenic amnesia and reckless/self-destructive behavior), raising questions regarding the adequacy of fit between these symptoms and the other core features of PTSD. Overall, findings suggest the DSM-5 model of PTSD is an improvement over the previous DSM-IV model of PTSD, but still may not represent the true underlying factor structure of PTSD.

Posttraumatic stress, heart rate variability, and the mediating role of behavioral health risks.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked to reduced heart rate variability (HRV), which is in turn a risk factor for cardiovascular disease and death. Although hyperarousal and anxiety are thought to underlie this association, behavioral health risks, including smoking, alcohol dependence, obesity, and sleep disturbance, represent potential mechanisms linking PTSD and HRV. METHODS: To test this hypothesis, short-term laboratory-based and 24-hour ambulatory measures of HRV were collected from 227 young adults (18-39 years), 107 of whom were diagnosed as having PTSD. Latent variable modeling was used to assess the relationship of PTSD symptoms with HRV along with potential behavioral health mediators. RESULTS: PTSD symptoms were associated with reduced HRV (ß = -0.21, p = .002). However, this association was reduced in models that adjusted for cigarette consumption and history of alcohol dependence and was rendered nonsignificant in a model adjusting for sleep disturbance. Independent mediation effects were deemed significant via bootstrapping analysis. Together, the three behavioral health factors (cigarette consumption, history of alcohol dependence, and sleep disturbance) accounted for 94% of the shared variance between PTSD symptoms and HRV. Abdominal obesity was not a significant mediator. CONCLUSIONS: These results indicate that behavioral factors-specifically smoking, alcohol overuse, and sleep disturbance-mediate the association between PTSD and HRV-based indices of autonomic nervous system dysregulation. Benefits from psychiatric and psychological interventions in PTSD may therefore be enhanced by including modification of health behaviors.

Sleep, fatigue, depression, and circadian activity rhythms in women with breast cancer before and after treatment: a 1-year longitudinal study.

PURPOSE: Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory. METHODS: Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year). RESULTS: Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own baseline levels and to NC (all p values <0.05). By 1 year, BC's fatigue, depressive symptoms, and QoL returned to baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC's. CONCLUSION: Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time.

Demand and modality of directed attention modulate "pre-attentive" sensory processes in schizophrenia patients and nonpsychiatric controls.

BACKGROUND: Mismatch negativity (MNN) and P3a are event related potential (ERP) measures of early sensory information processing. These components are usually conceptualized as being "pre-attentive" and therefore immune to changes with variations in attentional functioning. This study aimed to determine whether manipulations of attention influence the amplitudes and latencies of MMN and P3a and, if so, the extent to which these early sensory processes govern concurrent behavioral vigilance performance in schizophrenia patients and normal subjects. METHODS: Schizophrenia patients (SZ; n = 20) and Nonpsychiatric Control Subjects (NCS; n = 20) underwent auditory ERP testing to assess MMN and P3a across 4 EEG recording sessions in which attentional demand (low vs. high) and sensory modality of directed attention (visual vs. auditory) were experimentally varied. RESULTS: Across conditions, SZ patients exhibited deficits in MMN and P3a amplitudes. Significant amplitude and latency modulation were observed in both SZ and NCS but there were no group-by-condition interactions. The amount of MMN amplitude attenuation from low- to high-demand tasks was significantly associated with increased vigilance performance in both SZ and NCS groups (r = -0.67 and r = -0.60). Several other robust associations were also observed among neurophysiologic, clinical and cognitive variables. CONCLUSIONS: Attentional demand and modality of directed attention significantly influence the amplitude and latencies of "pre-attentive" ERP components in both SZ and NCS. Deficits in MMN and P3a were not "normalized" when attention was directed to the auditory stimuli in schizophrenia patients. The adaptive modulation of early sensory information processing appears to govern concurrent attentional task performance. The temporal window reflecting automatic sensory discrimination as indexed as MMN and P3a may serve as a gateway to some higher order cognitive operations necessary for psychosocial functioning.

Fatigue and Circadian Activity Rhythms in Breast Cancer Patients Before and After Chemotherapy: A Controlled Study.

BACKGROUND: Breast cancer (BC) patients often experience cancer-related fatigue (CRF) before, during, and after their chemotherapy. Circadian rhythms are 24-hour cycles of behavior and physiology that are generated by internal pacemakers and entrained by zeitgebers (e.g., light). A few studies have suggested a relationship between fatigue and circadian rhythms in some clinical populations. METHODS: One hundred and forty-eight women diagnosed with stage I-III breast cancer and scheduled to receive at least four cycles of adjuvant or neoadjuvant chemotherapy, and 61 controls (cancer-free healthy women) participated in this study. Data were collected before (Baseline) and after four cycles of chemotherapy (Cycle-4). Fatigue was assessed with the Short Form of Multidimensional Fatigue Symptom Inventory (MFSI-SF); circadian activity rhythm (CAR) was recorded with wrist actigraphy (six parameters included: amplitude, acrophase, mesor, up-mesor, down-mesor and F-statistic). A mixed model analysis was used to examine changes in fatigue and CAR parameters compared to controls, and to examine the longitudinal relationship between fatigue and CAR parameters in BC patients. RESULTS: More severe CRF (total and subscale scores) and disrupted CAR (amplitude, mesor and F-statistic) were observed in BC patients compared to controls at both Baseline and Cycle-4 (all p's<0.05); BC patients also experienced more fatigue and decreased amplitude and mesor, as well as delayed up-mesor time at Cycle-4 compared to Baseline (all p's<0.05). The increased total MFSI-SF scores were significantly associated with decreased amplitude, mesor and F-statistic (all p's<0.006). CONCLUSION: CRF exists and CAR is disrupted even before the start of chemotherapy. The significant relationship between CRF and CAR indicate possible underlying connections. Re-entraining the disturbed CAR using effective interventions such as bright light therapy might also improve CRF.

Prevention of quality-of-life deterioration with light therapy is associated with changes in fatigue in women with breast cancer undergoing chemotherapy.

PURPOSE: During chemotherapy, women with breast cancer not only experience poor quality of life (QOL), they also have little exposure to bright light, which has been shown to be associated with depression, fatigue, and poor sleep in other chronic illnesses. This study examined whether increased light exposure would have a positive effect on QOL. METHODS: Thirty-nine women with stage I-III breast cancer scheduled to receive ≥ 4 cycles of chemotherapy were randomized to a bright white light (BWL, n = 23) or dim red light (DRL, n = 16) treatment group. Data were collected before (baseline) and during cycles 1 and 4 of chemotherapy. Light was administered via a light box (Litebook(®), Ltd.). QOL was assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) and the Functional Outcomes of Sleep Questionnaire (FOSQ). RESULTS: Compared with baseline, the DRL group demonstrated significant decline in QOL during the treatment weeks of both cycles (all ps < 0.02), whereas the BWL group had no significant decline (all ps > 0.05). Mixed model analyses revealed that there was a group-by-time interaction for FOSQ at the treatment week of cycle 4, and this interaction was mediated by fatigue. CONCLUSION: The data suggest that increased exposure to bright light during chemotherapy may prevent the decline in QOL via preventing the increase in fatigue.

Decreased health-related quality of life in women with breast cancer is associated with poor sleep.

This study examined the longitudinal relation between health-related quality of life (HR-QOL) and subjective and objective sleep quality in 166 women with newly diagnosed Stage-1 through Stage-3 breast cancer, who were scheduled to receive ≥ 4 cycles of adjuvant/neoadjuvant chemotherapy. HR-QOL was assessed with the Medical Outcomes Study 36-item Short Form, Physical Component Scale (PCS), and Mental Component Scale (MCS) scores; subjective sleep was assessed with the Pittsburgh Sleep Quality Index; and objective sleep was measured with actigraphy. Data were collected before starting chemotherapy and during the last week of Cycle 4 of chemotherapy. Patients reported poor HR-QOL and poor sleep quality before and during chemotherapy. Short sleep time and long naps were recorded at both time points. The MCS score was related to reports of poor sleep, but not to recorded sleep; worse PCS scores were associated with reports of poor sleep and less recorded naptime, suggesting sleep plays an important role in cancer patients' HR-QOL.

Bright light therapy protects women from circadian rhythm desynchronization during chemotherapy for breast cancer.

Circadian rhythms (CRs) are commonly disrupted in women undergoing chemotherapy for breast cancer (BC). Bright light improves and strengthens CRs in other populations. This randomized controlled study examined the effect of morning administration of bright light therapy on CRs in women undergoing chemotherapy for BC. It was hypothesized that women receiving bright light therapy would exhibit more robust rhythms than women exposed to dim light. Thirty-nine women newly diagnosed with BC and scheduled for chemotherapy were randomized into 2 groups: bright white light (BWL) or dim red light (DRL). Women were instructed to use the light box every morning for 30 min during their first 4 cycles of chemotherapy. Wrist actigraphy was recorded at 5 time points: prior to chemotherapy (baseline), Cycle-1 treatment week (C1TW), Cycle-1 recovery week (C1RW), Cycle-4 treatment week (C4TW), and Cycle-4 recovery week (C4RW). There was a Group × Time interaction at C4TW compared to baseline such that the DRL group showed significant deterioration in the mean of the activity rhythm (mesor) and amplitude, whereas the BWL group exhibited a significant increase in both mesor and amplitude. The DRL group also exhibited significant deterioration in overall rhythm robustness at C1TW, C4TW, and C4RW. Women in the BWL group also showed significant decreases in overall rhythm robustness at C1TW and C4TW, but returned to baseline levels at both recovery weeks. The results suggest that morning administration of bright light may protect women from experiencing CR deterioration during chemotherapy.

Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy.

Fatigue and sleep disturbances are two of the most common and distressing symptoms reported by cancer patients. Fatigue and sleep are also correlated with each other. While fatigue has been reported to be associated with some inflammatory markers, data about the relationship between cancer-related sleep disturbances and inflammatory markers are limited. This study examined the relationship between fatigue and sleep, measured both subjectively and objectively, and inflammatory markers in a sample of breast cancer patients before and during chemotherapy. Fifty-three women with newly diagnosed stage I-III breast cancer scheduled to receive at least four 3-week cycles of chemotherapy participated in this longitudinal study. Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep was measured with actigraphy. Three inflammatory markers were examined: Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1RA) and C-reactive protein (CRP). Data were collected before (baseline) and during cycle 1 and cycle 4 of chemotherapy. Compared to baseline, more fatigue was reported, levels of IL-6 increased and IL-1RA decreased during chemotherapy. Reports of sleep quality remained poor. Mixed model analyses examining changes from baseline to each treatment time point revealed overall positive relationships between changes in total MFSI-SF scores and IL-6, between changes in total PSQI scores and IL-6 and IL-1RA, and between total wake time at night and CRP (all p's<0.05). These relationships suggest that cancer-related fatigue and sleep disturbances may share common underlying biochemical mechanisms.

The longitudinal relationship between fatigue and sleep in breast cancer patients undergoing chemotherapy.

STUDY OBJECTIVE: Fatigue and sleep disturbances are two of the most common and distressing symptoms of cancer patients. A relationship between the two symptoms was reported in symptom cluster studies; however, only subjective measurements of sleep were examined and most studies were cross-sectional. In this study of women with breast cancer undergoing chemotherapy, we explored the longitudinal relationship between fatigue and sleep measured both subjectively and objectively. DESIGN: Prospective study. Data were collected at 7 time points: before (baseline) and during the 3 weeks of cycle 1 and cycle 4 chemotherapy. PARTICIPANTS: Ninety-seven women with newly diagnosed stage I-III breast cancer who were scheduled to receive at least four 3-week cycles of chemotherapy. MEASUREMENT AND RESULTS: Objective sleep parameters were measured with an Actillume actigraph (Ambulatory Monitoring Inc.). Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Fatigue became worse during both cycles of chemotherapy (P-values < 0.01). Subjective sleep quality was poor at baseline and remained unchanged throughout treatment. Objective nighttime and daytime total sleep time increased compared to baseline during the treatment administration week of both cycles; daytime total wake time decreased during the treatment week of both cycles and during the last 2 week of cycle 4. Mixed model results revealed that fatigue was positively associated with total PSQI scores and with objective measures of total nap time, and negatively associated with total wake time during the day (all P-values < 0.01). CONCLUSION: Fatigue was significantly associated with subjective reports of poor sleep and objective measures of daytime sleepiness, but not with nocturnal sleep as measured with actigraphy. This relationship between fatigue and sleep warrants further studies to explore their possible common underlying etiology.

Light treatment prevents fatigue in women undergoing chemotherapy for breast cancer.

PURPOSE: Fatigue is one of the most disturbing complaints of cancer patients and is often the reason for discontinuing treatment. This randomized controlled study tested the hypothesis that increased morning bright light, compared to dim light, would result in less fatigue in women with breast cancer undergoing chemotherapy. METHODS: Thirty-nine women newly diagnosed with stage I-III breast cancer were randomized to either bright white light (BWL) or dim red light (DRL) treatment and were instructed to use the light box for 30 min every morning throughout the first four cycles of chemotherapy. The Multidimensional Fatigue Symptom Inventory was administered prior to the start of chemotherapy (baseline), during the chemotherapy treatment week of cycle 1 (C1TW), the last week (recovery week) of cycle 1 (C1RW), the chemotherapy treatment week of cycle 4 (C4TW), and the last week (recovery week) of cycle 4 (C4RW). RESULTS: The DRL group reported increased fatigue at C1TW (p = 0.003) and C4TW (p < 0.001) compared to baseline, while there was no significant change from baseline in the BWL group. A secondary analysis showed that the increases in fatigue levels in the DRL group were not mediated through nor associated with changes in sleep or in circadian rhythms as measured with wrist actigraphy. CONCLUSIONS: The results of this study suggest that morning bright light treatment may prevent overall fatigue from worsening during chemotherapy. Although our hypothesis that overall fatigue would improve with bright light treatment was not supported, the lack of deterioration in total fatigue scores suggests that bright morning light may be a useful intervention during chemotherapy for breast cancer.

The Symptom Cluster of Sleep, Fatigue and Depressive Symptoms in Breast Cancer Patients: Severity of the Problem and Treatment Options.

Breast cancer is the most commonly diagnosed cancer in women. Insomnia is a significant problem in breast cancer patients, affecting between 20% to 70% of newly diagnosed or recently treated cancer patients. Pain, fatigue, anxiety, and depression are also common conditions in breast cancer and often co-occur with insomnia in symptom clusters, exacerbating one another, and decreasing quality of life (QOL). There have been no clinical trials of drugs for sleep in cancer. Cognitive behavioral psychotherapies on the other hand, have shown some of the most positive results in alleviating the distressing symptoms that often accompany the breast cancer experience, but even these studies have not targeted the symptom cluster. Pharmacological as well as non-pharmacological treatments need to be explored. It might be that a combined pharmacological and behavioral treatment is most efficacious. In short, substantially more research is needed to fully understand and treat the symptom cluster of insomnia, fatigue, pain, depression and anxiety in breast cancer.