According to recent research, the majority of breast cancer metastatic spread happens when people are asleep. The researchers called this finding "shocking and surprising."
Nicola Aceto, Ph.D., professor of molecular oncology at the Swiss Federal Institute of Technology (ETH) Zurich, Switzerland, told Medscape Medical News that "this has not been proven previously [and] we were shocked, surely."
According to the authors, the findings might have an impact on whether to do a biopsy and how to treat malignancies that are likely to metastasize.
On June 22, the journal Nature published the findings online.
Circulating tumor cells (CTC) are thought to be shed continuously or after certain occurrences like surgery or physical exertion, but the mechanisms governing tumor cell metastasis and how circadian cycles may affect carcinogenesis are yet untold.
Aceto and colleagues took blood samples from 30 breast cancer patients at 4:00 AM and 10:00 AM, which correspond to the body's resting and active phases, respectively, to better understand the processes.
The study team found that samples taken during the resting period included more than 78% of all circulating tumor cells.
This discovery is amazing, write Ph.D. candidates Harrison Ball and Sunitha Nagrath from the University of Michigan in Ann Arbor in Nature News & Views.
Aceto and coworkers discovered that circulating tumor cells produced at night divide more quickly and have a higher potential to metastasize in comparison to those produced during the day, which, in their words, "are devoid of metastatic abilities." They also found that similar findings were made in a number of mouse models.
The team also found that insulin promotes tumor cell proliferation in a time-dependent manner and that key circadian rhythm hormones (such as melatonin, testosterone, and glucocorticoids) regulate the generation of circulating tumor cells. These findings point to the need for "time-controlled approaches for the characterization and treatment of breast cancer.
"The results indicating [circulating tumor cell] multiplication and release during the rest phase imply that clinicians may need to become more aware of when to deliver certain medications.
However, both stress that major clinical trials would be required before any consideration of circadian rhythms would be adopted into normal therapy. It's also uncertain if these findings in breast cancer apply to other types of tumors.
Mariana G. Figueiro, Ph.D., who was not involved in the study, says that if studies show that metastatic spread occurs more frequently at night, "there is a chance to treat patients at crucial times."
Figueiro, of the Icahn School of Medicine at Mount Sinai in New York City, sees a possible influence on blood draw scheduling as well. "I think it's vital to tighten up on how people conduct biopsies and bloodwork depending on circadian time," she added.
Marleen Meyers, MD, concurs that these discoveries have several clinical implications.
"The most evident is that the time of day [that] medication is provided may affect efficacy," said Meyers, clinical professor of medicine at New York University Langone's Perlmutter Cancer Center.
However, Meyers pointed out that the benefits of treating someone at night would have to be balanced against the disadvantages of disrupting a person's regular sleep-wake cycle. "If this discovery is clinically significant, implementing it into clinical care will be difficult," she added.
There was no mention of financing for the study. Aceto is a co-founder and board member of PAGE Therapeutics AG in Switzerland, a named inventor in patent filings linked to tumor cell circulation, a paid consultant for multiple firms, and a Novartis shareholder. PAGE Therapeutics AG, Switzerland, is co-founded by co-author Christoph Rochlitz, MD. The other authors have declared that they have no conflicting interests. Meyers and Figueiro have no relevant financial connections to disclose.
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