Do breast cancer cells ‘awaken’ at night?
These cancer cells wake up when people sleep
Cancer is at its deadliest when tumour cells worm their way into a person’s blood stream and travel to a new site in the body where they take root and start growing again. This process, known as metastasis, kills about 90 per cent of cancer victims within five years of diagnosis.
Now, researchers say they’ve discovered why this happens – and it has nothing to do with the hours of daylight. Circulating tumour cells, or CTCs, are most active when people are asleep, according to a study published today in Nature Communications.
CTCs are tiny fragments of tumour cells that circulate throughout the body and can give doctors vital information about whether a patient’s disease has spread. They’re found in the blood, bone marrow, lymph nodes and even semen.
But while scientists have theorised that the circadian clock might influence the behaviour of these cells, no one had actually looked for evidence of it.
So, the team used a technique called single cell RNA sequencing to analyse hundreds of thousands of genes expressed in individual CTCs isolated from the blood of 10 women with breast cancer.
They found that CTCs express different sets of genes depending on what part of the 24 hour cycle they’re coming from. In particular, they were most active around midnight, a finding that aligns with previous studies showing that people tend to go to bed later in the evening.
The findings suggest that tumour cells “wake up” when people are sleeping, says co-author Professor Nicola Aceto, a researcher at the Swiss Federal Institute for Technology in Zurich.
Cancer on the clock
The study found that patients’ circulating tumour cells (CTCs), which are shed into the bloodstream during the course of disease, showed different patterns based on whether they were tested early in the morning or late afternoon.
In particular, CTCs collected around midnight seemed to show less aggressive behaviour than those taken later in the day.
This finding suggests that the timing of treatment could influence how well it works, according to the researchers. “If you treat patients when their CTCs are low, you’re probably going to see better outcomes,” Aceto says.
Sleep is not the enemy
Hormone levels change throughout the day, sometimes even within minutes. And while scientists know that changes in hormone levels affect cell activity, they don’t fully understand why some tumors grow faster during certain times of day.
But researchers think circadian rhythm plays a role. “The timing of our daily activities is controlled by 24-hour cycles,” explains study coauthor Daniel Aceto, PhD, director of the Center for Circadian Biology at Weill Cornell Medicine. “This includes sleeping patterns.”
In the study, published today in Cell Reports, researchers analyzed data from mouse models of breast cancer and discovered that tumor growth rates fluctuate throughout the day. They found that when estrogen levels drop, the number of circulating tumor cells increases. When estrogen levels increase, however, fewer circulating tumor cells are present.
Researchers think the reason behind this phenomenon is that when estrogen levels decrease, the body produces less of a protein called PER2, which helps regulate circadian rhythms. This leads to increased tumor growth because the body doesn’t produce enough PER2 to keep the clock ticking. But when estrogen levels rise, the body makes more PER2, which slows down tumor growth.
To test whether PER2 affects tumor growth in humans, the researchers turned to blood samples collected from women with stage I or II breast cancer. They found that the amount of PER2 in patients’ blood correlated with tumor size.
While the findings suggest that PER2 influences tumor growth, there are many questions left unanswered. For example, what causes the fluctuations in estrogen levels? What happens to PER2 levels in breast cancer patients over time? Does manipulating PER2 levels affect tumor growth?
Aceto says we’re just beginning to unravel the complex relationship between circadian rhythms and cancer. He hopes that understanding the connection will help us develop new ways to treat disease and improve quality of life for people living with cancer.
Long stretches of shift work may increase cancer risk.
A study published Tuesday in JAMA Internal Medicine found that women who worked night shifts for four or five nights per week had a 35% increased chance of developing colorectal cancer compared to those who did not work night shifts. This increased risk was seen among both smokers and nonsmokers. Women who worked six nights per week during the same period had a 50% greater chance of developing ovarian cancer. A similar pattern was observed in men.
The researchers believe that exposure to light at night disrupts the circadian rhythm, which regulates many biological processes such as metabolism and hormone production. Previous studies have shown that disrupted circadian rhythms are associated with obesity and diabetes. However, the current research suggests that disruptions in circadian rhythms may play a role in cancer development beyond just weight gain and metabolic disorders.
This study does not prove that working long hours causes cancer, nor does it imply that people should avoid night shifts altogether. But it does suggest that there is a potential link between prolonged shift work and certain types of cancer.
Cancer therapy side effects and emotions can disrupt sleep.
Sleep deprivation is one of the most common symptoms among people undergoing cancer treatments. A study published in JAMA Internal Medicine found that nearly half of patients reported insomnia, difficulty sleeping because of pain, and trouble falling asleep while receiving chemotherapy. Other studies suggest that up to 70% of breast cancer survivors experience insomnia following surgery.
Anxiety, depression, deep fatigue and digestive-system problems are some of the other conditions that can interfere with sleep. In addition, women with breast cancer report high rates of sexual dysfunction, including painful intercourse, vaginal dryness and low libido; men with prostate cancer report erectile dysfunction.
Tell your doctor about your lack or sleep. If you’re experiencing insomnia, ask whether it could be related to cancer. You might also want to consider asking for a referral to a mental health professional if you feel like you need help managing stress or dealing with emotional issues.
Relaxation techniques and cognitive behavioral therapies can help. Try meditation, yoga, progressive muscle relaxation, mindfulness, hypnosis, guided imagery, biofeedback, massage, aromatherapy, music therapy, art therapy and creative writing.
Stick to a regular bedtime. Avoid napping in the afternoon, especially if you’re tired. And don’t nap during the day unless you have a medical reason to do so.
Also, try to limit caffeine. Many medications cause drowsiness, including antihistamines, antidepressants and certain blood pressure medicines.
Try to avoid alcohol, nicotine and sedatives. These substances can make it harder to fall asleep.
Insomnia can bother cancer survivors for years and even decades.
Sleep problems affect everyone differently. But researchers say cancer patients often struggle with insomnia — a chronic inability to fall asleep or stay asleep. And it can take years for survivors to recover.
Researchers at Boston Children’s Hospital wanted to learn more about how insomnia affects children and adolescents with cancer. So they asked kids with leukemia and lymphoma to wear actigraphy devices for one week. Actigraphy measures movement over time, allowing scientists to see if people slept well during the night.
The study found that many kids had trouble sleeping. They spent less time in deep sleep and more time awake after falling asleep. Kids with cancer also reported feeling tired all day, even though they didn’t feel sleepy.
What you can do:
Do some research. Talk to your doctor about what might be affecting your sleep. You may find tips online, like:
• Avoid caffeine after noon.
• Don’t drink alcohol within four hours of bedtime.
Cancer Survivors May Deal With Sleep-Disordered Breathing
Sleep-disordered breathing affects about 20 percent of adults over age 65, according to the Centers for Disease Control and Prevention. But researchers don’t know how many adult cancer survivors suffer from it because most studies focus on children. A Johns Hopkins University team looked at data from 558 pediatric cancer patients treated between 2000 and 2010. They found that 19 percent had sleep-disordered breathing—a number that rose to 39 percent among those who received cranial radiation therapy.
The researchers say there are several reasons why sleep apnea might occur more often in cancer survivors. Cancer treatments like chemotherapy and radiotherapy can damage nerves and disrupt normal breathing patterns. Chemicals used in some medications can cause dry mouth, making it harder to breathe while sleeping. And tumors themselves can interfere with airway function.