Circadian Rhythm and Concentration of Melatonin in Breast Cancer Patients

Background: Melatonin is a biomarker of the central circadian clock and its chronobiotic actions entraining circadian rhythms to the light-dark cycle are well known. Reduction in melatonin levels and altered circadian rhythms have been associated with a high risk of breast cancer. Melatonin has also been shown to display anti-proliferative effects on breast cancer growth and proliferation. Evaluation of melatonin circadian rhythm alterations in patients bearing breast cancer may have inter-esting prognostic and therapeutic applications. Objective: To review studies evaluating the circadian rhythm of melatonin in breast cancer patients. The effects of surgery and chemotherapy on melatonin secretion were also reviewed. Methods: Electronic databases, including PubMed/MEDLINE and Scopus, were searched from their inception to May 2020, using the keywords "Melatonin", "Circadian rhythm" and "Breast cancer". Results: Patients with breast cancer maintain a circadian rhythm of melatonin secretion with relatively high levels during the night and low levels during the day, however, a reduction in nocturnal melatonin peak and decreased amplitude of melatonin circadian rhythms in these patients have also been re-ported. Melatonin levels can influence estrogen receptor concentrations in hormone-dependent estro-gen-positive breast cancer. Chemotherapy alters melatonin levels and breast surgery tends to alter melatonin secretion at first-day post-operation. Melatonin levels correlate with clinical and psycho-logical symptoms of breast cancer, such as sleep quality and depression severity. Conclusion: Circadian rhythm and the concentration of melatonin in the blood are altered in patients with breast cancers, and it can modify not only the sleep-wake cycle and, thus, patients' quality of life but due to melatonin's antioxidant effects, the effect of therapies can be modulated. Due to the hetero-gonous protocols used to assess melatonin and variable environmental factors during sampling, further studies need to control, such variables in order to tailor clinical trials based on melatonin rhythm ad-justment and/or supplementation in breast cancer patients.