“The brain is an exquisite sensor of what’s going on in your body,” says Cold Spring Harbor Laboratory Assistant Professor Jeremy Borniger. “But it requires balance. Neurons need to be active or inactive at the right times. If that rhythm goes out of sync even a little bit, it can change the function of the entire brain.”

That balance relies on carefully timed patterns of activity. When those patterns slip, even slightly, the brain’s ability to regulate the body can be disrupted in wide-ranging ways.

Breast Cancer Alters Daily Stress Hormone Cycles

In studies involving mice, Borniger’s lab discovered that breast cancer interferes with normal diurnal rhythms, meaning the natural day and night cycle of stress hormone release. In rodents, this hormone is corticosterone. 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 stayed unnaturally even. This loss of rhythm was linked to poorer quality of life and higher mortality in the mice.

Early Disruption of the Brain’s Stress System

Disrupted daily rhythms are already known to contribute to stress-related problems such as insomnia and anxiety, which are common among people with cancer. 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 on a healthy schedule.

What surprised Borniger was how early this disruption appeared. In mice, breast cancer altered stress hormone rhythms before tumors could be physically detected. “Even before the tumors were palpable, we see about a 40 or 50% blunting of this corticosterone rhythm,” he said. “We could see that happening within three days of inducing the cancer, which was very interesting.”

Resetting Brain Rhythms Restores Immune Response

Closer examination of the hypothalamus revealed that certain neurons were stuck in a state of constant activity but produced weak signals. When researchers stimulated these neurons to recreate a normal day and night pattern, stress hormone rhythms returned to normal.

This reset had a striking effect. Anti-cancer immune cells began moving into breast tumors, and the tumors shrank substantially. Borniger explains:

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

Improving Physiology to Support Cancer Treatment

The research team is now working to understand how tumors disrupt the body’s normal rhythms in the first place. Borniger believes this line of research could eventually strengthen existing cancer treatments.

“What’s really cool is that we didn’t treat the mice with anti-cancer drugs,” he says. “We’re focused on making sure the patient is physiologically as healthy as possible. That itself fights the cancer. This might one day help boost the effectiveness of existing treatment strategies and significantly reduce the toxicity of many of these therapies.”



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