Sleeping in the presence of dim bedroom light, exposure to street light at night, and chronically disrupted sleep each have been linked to increased breast cancer risk and may be associated with worse survival. The hormone melatonin is produced at night (or in conditions of darkness) and nocturnal light disrupts melatonin synthesis.
Melatonin communicates information concerning available light to various organs and is involved in the regulation of circadian rhythms. Now a new study presented at the 2020 Annual Meeting of the American Association for Cancer Research (AACR) has reported that circadian melatonin signal disruption caused by light at night increased metastasis to the bone in a mouse model of hormone receptor positive (ER+/PR+) breast cancer. Administration of melatonin partially counteracted this effect.
Circadian rhythm disruption and breast cancer
As noted above, sleeping in the presence of artificial light inhibits the production of melatonin, a hormone which is vital to the regulation of circadian rhythms, daily 24-hour cycles that control most physiologic processes. Circadian synchronization depends on an internal clock that is synchronized to light-dark cycles. Circadian rhythms are popularly thought of as being driven solely by the master clock in the brain, which receives information directly concerning light-dark conditions through the eyes. However, individual cells in organs apart from the brain also have clocks. Note that blue light wavelengths appear to have a far greater suppressive effect on melatonin production than red wavelengths.
Latest research finds dim light at night promotes bone mets
The study referenced above was designed to test the hypothesis that circadian disruption caused by dim light at night promotes breast cancer bone metastasis. The authors previously demonstrated that such disruption of melatonin signaling can significantly heighten the metastatic potential of breast cancer cells. In that study, human breast tumor xenografts grown in female rats exposed to alternating cycles of 12 hours of light during daytime hours and 12 hours of dim light at night (which suppressed melatonin production), developed resistance to Adriamycin chemotherapy. Significantly, administration of nocturnal melatonin reduced tumor growth and Adriamycin resistance.
In the current study, moderately metastatic luminal A estrogen receptor alpha (ERα) positive MCF-7 breast cancer cells were inoculated into the tibia (shinbone) of athymic nude mice to mimic metastatic bone disease. The mice were housed under dim light conditions at night, which suppressed nocturnal melatonin production. The animals developed substantial metastatic bone tumors that were highly osteolytic (i.e., characterized by destruction of normal bone, which is typical of breast cancer bone metastases).
Administering melatonin to the mice at dosages designed to mimic levels under normal functioning partially reduced the bone tumor burden. In addition, the melatonin receptor antagonist luzindole was shown to block the inhibitory effect of night time melatonin on metastatic tumor growth, thus demonstrating a receptor-mediated mechanism. The authors conclude that intact night time melatonin anti-cancer signaling is important in suppressing bone metastatic tumor growth. The results provide a rationale for the development of circadian-optimized melatonin therapy to improve the survival rates of breast cancer patients with bone metastases, according to the authors.
Please see our circadian rhythms and melatonin tags for more information.