Breast cancer may disrupt the natural rhythms of stress hormones in the brain, according to new research from Cold Spring Harbor Laboratory. The study, led by Assistant Professor Jeremy Borniger, examined how breast cancer affects corticosterone levels—the main stress hormone in rodents—in mice models.
Borniger explained the significance of these findings: "The brain is an exquisite sensor of what's going on in your body. 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."
Under normal conditions, corticosterone levels rise and fall throughout the day. In humans, this hormone is called cortisol. The research team found that breast cancer flattens these daily fluctuations, which can lead to reduced quality of life and increased mortality.
Disruptions in diurnal rhythms are linked to common stress responses such as insomnia and anxiety—issues frequently experienced by cancer patients. The body uses a feedback loop known as the HPA axis (hypothalamus-pituitary-adrenal axis) to regulate healthy stress hormone cycles. Borniger noted that changes were observed before tumors became detectable: "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."
The researchers discovered that key neurons in the hypothalamus became hyperactive but produced low output when exposed to breast cancer cells. By stimulating these neurons to follow a normal day-night cycle again, they restored regular stress hormone rhythms in mice. This adjustment also encouraged anti-cancer immune cells to enter breast tumors and caused significant tumor shrinkage.
Borniger described their observations: "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."
The research group continues investigating how tumors disturb bodily rhythms with hopes for future therapeutic advances.
"What's really cool is that we didn't treat the mice with anti-cancer drugs," Borniger said. "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."
