Breast cancer patients have progressively impaired sleep-wake activity rhythms during chemotherapy

Abstract

Purpose: Prior cross-sectional studies have shown that cancer patients have sleep-wake activity cycles that show little distinction between daytime and nighttime, a pattern indicative of circadian disruption. This pattern is seen both before and during cancer treatment. Long-term data are needed, however, to assess to what extent circadian rhythm impairments evolve over the course of chemotherapy. The goal of this study was to assess the longitudinal course of sleep-wake activity rhythms before and during chemotherapy for breast cancer.

Patients and methods: Ninety-five women scheduled to receive neoadjuvant or adjuvant anthracycline based chemotherapy for a stage I-III breast cancer participated. The participants wore a wrist actigraph for 72 consecutive hours at baseline (pre-chemotherapy), as well as during the weeks 1, 2 and 3 (W1, W2, W3) of cycle 1 and cycle 4 of chemotherapy. Sleep-wake circadian activity variables were computed based on actigraphic data.

Results: Compared to baseline, with the exception of acrophase, all circadian rhythm variables examined, including amplitude, mesor, up-mesor, down-mesor, and rhythmicity were significantly impaired during the first week of both chemotherapy cycles. Although the circadian variables approached baseline values during W2 and W3 of cycle 1, most remained significantly more impaired during W2 and W3 of cycle 4.

Conclusion: These data suggest that the first administration of chemotherapy is associated with transient disruption of sleep-wake rhythm, while repeated administration of chemotherapy results in progressively worse and more enduring impairments in sleep-wake activity rhythms.

Figure 1

Screening and enrollment flowchart

Figure 2

One participant's raw actigraph data for 3 days during each time point of data collection. Double plot with the first row representing day 1 (midnight to midnight) and day 2 (midnight to midnight), the second row representing day 2 again followed by day 3 and so on. This patient had a robust circadian rhythm at baseline with a clear contrast between daytime and nighttime activity, minimal body movements during the night, and constant bedtime and wake time across the 3 nights. At cycle 1, the rhythm became disrupted with less constant bedtime and wake time and more activity during the night, a pattern that was aggravated at cycle 4 where the contrast between daytime and nighttime is less clear, particularly during week 1. Red bars = missing data (off wrist).

Figure 3

Means (and standard errors) obtained on each circadian rhythm variable, at each time assessment. *P < 0.05; **P < 0.01; ***P < 0.001; ***P < 0.0001 for comparisons between each time point vs. baseline.