Breast cancer is highly treatable in the early stages before the disease starts spreading. Once the cancer cells have metastasized to other parts of the body, however, the disease becomes harder to treat. The metastatic spread of cancer is achieved by the movement of circulating tumor cells (CTCs) through the bloodstream.
Before now, researchers believe that the CTCs are continuously shedding from growing tumor cells. However, a striking and unexpected discovery by some Swiss researchers has found that CTCs are more prone to metastasize during a body’s resting phase. This study found that breast cancer metastasized far more efficiently during sleep.
According to Nicola Aceto, Ph.D. of the Swiss Federal Institute of Technology in Zurich, and colleagues, there’s a “striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep.”
The study investigated a group of 30 women, 21 of these women had early (non-metastatic) breast cancer, and the rest (9) were in the late metastatic stages of the disease (stage IV).
The researchers collected blood samples from these patients at two points: during the body’s resting phase (4am) and the active phase (10am). They learned that 78.3% of the CTC was found in the blood samples obtained at night time during the body’s resting phase.
Astonished by this result, the researchers then tested the effect using mice models of breast cancer cells. Mice have an inverted circadian rhythm compared to humans. The researchers found that most CTCs (up to 88% higher than the baseline) were found in samples taken during the daylight hours when the mice are resting.
The researchers also monitored the CTC levels when the sleep pattern of the mice was disrupted by administering melatonin or altering the light cycles and found that the CTC levels were highest while the mice were resting.
In addition, the researchers further investigated the capacities of CTCs obtained at different circadian rhythm phases to metastasize. To do this, they injected the resting- and active-phase CTCs into healthy, tumor-free mice during various phases of their circadian cycles. It was found that the CTC from the rest phase “exhibit an extraordinary metastasis-forming capacity” compared to those obtained during an active phase.
According to researchers, “The evidence suggests that a more holistic approach to studying CTCs, including harnessing technologies for continuous in vivo monitoring, might be necessary to understand the dynamics of cancer metastasis fully.”