Breast Cancer Spreads More Aggressively at Night

The disease awakens and begins to spread when women with metastatic breast cancer close their eyes at night.

That is the startling conclusion of a report that was published in Nature this week, debunking the notion that breast cancer metastasis occurs at a constant pace all the time.

The outcome, according to the researchers, may alter future blood samples taken from cancer patients by medical professionals.

"In our view, these findings may indicate the need for healthcare professionals to systematically record the time at which they perform biopsies," says ETH Zurich's professor of molecular oncology and senior author Nicola Aceto.

"It may help to make the data truly comparable."

When examining samples at various times of the day, researchers found an inexplicable variation in the quantity of circulating tumor cells. This observation led them to the issue at hand.

"Some of my colleagues work early in the morning or late in the evening; sometimes they'll also analyze blood at unusual hours," according to Aceto.

Another indication came from mice, which sleep during the day when blood samples are most frequently obtained, and which appeared to have a considerably larger amount of circulating cancer cells than people.

The Swiss researchers examined 30 breast cancer patients to see what was happening (21 patients with early breast cancer that had not metastasized and nine patients with stage IV metastatic disease).

They discovered "a striking and unexpected pattern": The majority of circulating tumor cells (78.3%) were discovered in blood samples collected at night compared to a substantially lower percentage in those collected during the day.

The similar outcome was discovered when the researchers gave mice injections of breast cancer cells and collected blood samples throughout the day. When the animal was at rest, there were significantly more circulating tumor cells.

Intriguingly, the researchers found that the cancer cells they had gathered during the resting phase were "highly prone to metastasize, whereas circulating tumor cells generated during the active phase are devoid of metastatic ability".

The expression of mitotic genes was elevated in tumor cells collected from mice and people that were at rest, according to genetic study. As mitotic genes regulate cell division, this enhances their capacity for metastasizing.

By altering the mice's light-dark cycle, the researchers conducted trials where they gave some animals jet lag. Mice with altered circadian rhythms had much less circulating tumor cells than control mice.

In a further experiment, the researchers looked at how hormones comparable to those produced while mice are awake could alter the quantity of tumor cells that circulate in the blood when the animal is at rest.

They administered dexamethasone, testosterone, and insulin (a hormone that enables the conversion of sugar into energy) to mice (a synthetic chemical that acts like cortisol, the stress hormone).

A blood sample collected during the rest period revealed a "marked reduction" in the amount of circulating tumor cells, according to the researchers (when the tumor would normally be most aggressive).

"Our research shows that the escape of circulating cancer cells from the original tumor is controlled by hormones such as melatonin, which determine our rhythms of day and night," says ETH Zurich molecular oncology expert and the study's primary author, Zoi Diamantopoulou.

This paper was published in Nature.