Bedtime misalignment and progression of breast cancer

Abstract

Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness–Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes (“going to bed at preferred bedtime”) (n=72), and 46.9 months for women with misaligned bedtimes (“going to bed later or earlier than the preferred bedtime”) (n=13) (log rank p=0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR=0.539, 95% CI=0.320–0.906, p=0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR=2.169, 95% CI=1.124–4.187, p=0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR=1.641, 95% CI=1.000–2.695, p=0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR=3.180, 95% CI=1.327–7.616, p=0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms.

Exercise in patients coping with breast cancer: An overview

“…Hahm et al [26] showed that disruption of the circadian rhythm, such as by performing night shift work, might have an association with the progression of breast cancer. Exercise also acts as a regulator on the circadian rhythm and sleep; therefore regular exercise might hypothetically have an indirect effect on preventing the progression of breast cancer.…”

DNA damage and the circadian clock

“…Results suppor ng the data from mouse models were obtained in human studies as well. Specifically, chronic bed me misalignment was found to be associated with faster tumour progression in pa ents with breast cancer [35]. Tumour progression was also accelerated in mice subjected to experimental condi ons imita ng chronic jet lag [225].…”

“…Circadian misalignment may be associated with increased risk for development of insulin resistance (metabolic syndrome, diabetes type 2) [28]; various cancers (breast cancer, prostate cancer, colorectal cancer, and others) [29][30][31]; arterial hypertension; cardiac arrhythmia [32][33][34] in other words, many of the diseases of middle and advanced age'. When the cancer had already developed, chronic disrup on of the circadian rhythms may some mes accelerate its progression and/or increase the risk for metastasising [30,35] (for details, see below).…”

Endocrine Effects of Circadian Disruption

“…Epidemiological studies indicate that breast cancer risk is significantly elevated in industrialized societies and that this risk increases as countries become more westernized. Misalignment of bedtime on a daily basis, which is an indication of social jetlag and circadian disruption, is associated with more rapid breast cancer development (121). Nighttime light levels also codistribute with breast cancer incidents (122).…”