Michelle Rissling

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 ps<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.

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 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 ps < 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 ps < 0.05). The increased total MFSI–SF scores were significantly associated with decreased amplitude, mesor and F-statistic (all ps < 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.