Scientists have discovered that breast cancer can disrupt the brain’s internal clock almost immediately after the onset of cancer, without anyone noticing. In mice, tumors flattened the natural daily rhythm of stress hormones, disrupting the feedback loop between the brain and body that regulates stress, sleep, and immunity. Remarkably, when the researchers restored the correct day-night rhythm in certain brain neurons, the stress hormone cycles returned, immune cells flooded into the tumors, and the cancerous lesions shrank—without the use of cancer drugs.

“The brain is an extremely sensitive sensor for everything that goes on in your body,” says Jeremy Borniger, assistant professor at Cold Spring Harbor Laboratory. “But it needs balance. Neurons must be active or inactive at the right time. If this rhythm is even slightly out of balance, it can alter the function of the entire brain.” This balance depends on carefully coordinated patterns of activity. If these patterns deviate even slightly, the brain’s ability to regulate the body can be disrupted in many ways.

Breast Cancer Alters the Daily Stress Hormone Cycle

In breast cancer, the daily stress hormone cycle, especially that of cortisol, is often altered. While cortisol rises sharply in healthy people in the morning after waking up and falls continuously throughout the day, many breast cancer patients show a flattened daily pattern. The morning cortisol rise is often weakened or delayed, while cortisol levels remain elevated in the evening and at night. As a result, the normal difference between high morning and low evening levels is lost.

These changes are mainly caused by chronic activation of the stress axis. The psychological stress caused by diagnosis and therapy, persistent anxiety and sleep disorders, as well as inflammatory processes originating from the tumor, influence the regulation of the hypothalamic-pituitary-adrenal axis. Cancer therapies can also further disrupt the cortisol rhythm. A permanently altered stress hormone cycle is associated with pronounced fatigue, sleep problems, and impaired immune function, and has been linked in some studies to a less favorable disease progression.

In studies on mice, Borniger’s laboratory discovered that breast cancer disrupts the normal circadian rhythm, i.e., the natural day-night cycle of stress hormone release. In rodents, this hormone is corticosterone, while in humans it is cortisol. Under healthy conditions, these hormone levels rise and fall at predictable times throughout the day. The researchers found that breast tumors flattened this normal pattern. Instead of fluctuating, corticosterone levels remained unnaturally steady. This loss of rhythm was associated with poorer quality of life and higher mortality in the mice.

Resetting Brain Rhythms Restores Immune Response

It is already known that disrupted circadian rhythms contribute to stress-related problems such as insomnia and anxiety, which are common in cancer patients. These rhythms are regulated by a feedback network known as the HPA axis. The hypothalamus (H), pituitary gland (P), and adrenal glands (A) work together to keep stress hormones in a healthy rhythm.

What surprised Borniger was how early this disruption occurred. In mice, breast cancer altered the stress hormone rhythm before tumors were physically detectable. “Even before the tumors were palpable, we observed a 40 to 50% attenuation of this corticosterone rhythm,” he said. “We were able to observe this within three days of triggering the cancer, which was very interesting.”

Improving Physiology to Support Cancer Treatment

A closer examination of the hypothalamus (a control center in the brain that brings together external stimuli, internal body states, and emotional information and uses nerve and hormone signals to keep the body in balance) revealed that certain neurons were stuck in a state of constant activity but were producing only weak signals. When the researchers stimulated these neurons to restore a normal day-night pattern, stress hormone rhythms returned to normal. This reset had a remarkable effect. Anti-cancer immune cells began to invade the breast tumors, and the tumors shrank significantly. Borniger explains:

“Enforcing this rhythm at the right time of day increased the immune system’s ability to fight cancer—which is very strange, and we’re still trying to figure out exactly how it works. The interesting thing is that the same stimulation at the wrong time of day no longer has this effect. So you really have to have this rhythm at the right time to achieve this anti-cancer effect.“

The research team is now working to understand how tumors disrupt the body’s normal rhythm in the first place. Borniger believes that this line of research could ultimately strengthen existing cancer treatments. ”The really cool thing about this is that we didn’t treat the mice with cancer drugs,” he says. “We focus on ensuring that the patient is as physiologically healthy as possible. That alone already fights the cancer. This could one day help to increase the effectiveness of existing treatment strategies and significantly reduce the toxicity of many of these therapies.”