Altered Circadian Rhythms and Breast Cancer: From the Human to the Molecular Level

Hui-Hsien Lin, Michelle E. Farkas

Circadian clocks are fundamental, time-tracking systems that allow organisms to adapt to the appropriate time of day and drive many physiological and cellular processes. Altered circadian rhythms can result from night-shift work, chronic jet lag, exposure to bright lights at night, or other conditioning, and have been shown to lead to increased likelihood of cancer, metabolic and cardiovascular diseases, and immune dysregulation. In cases of cancer, worse patient prognoses and drug resistance during treatment have also been observed. Breast, colon, prostate, lung, and ovarian cancers and hepatocellular carcinoma have all been linked in one way or another with altered circadian rhythms. Critical elements at the molecular level of the circadian system have been associated with cancer, but there have been fairly few studies in this regard. In this mini-review, we specifically focus on the role of altered circadian rhythms in breast cancer, providing an overview of studies performed at the epidemiological level through assessments made in animal and cellular models of the disease. We also address the disparities present among studies that take into account the rhythmicity of core clock and other proteins, and those which do not, and offer insights to the use of small molecules for studying the connections between circadian rhythms and cancer. This article will provide the reader with a concise, but thorough account of the research landscape as it pertains to altered circadian rhythms and breast cancer.