Summary: Breast cancer can rapidly derail the brain’s day-night regulation of stress hormones, even before tumors are detectable. In mice, the disease flattens normal corticosterone rhythms by altering hypothalamic neuron activity, which may worsen outcomes and mimic symptoms often seen in cancer patients, such as insomnia and anxiety.
Restoring the brain’s natural rhythm reopened healthy stress-hormone cycles and unexpectedly boosted the immune system’s ability to shrink tumors. The work suggests that stabilizing bodily rhythms—not just targeting tumors—could enhance cancer treatment and improve quality of life.
Key Facts:
- Hormone Rhythm Disruption: Breast cancer blunts normal day-night stress-hormone rhythms by 40–50% in just three days.
- Neural Mechanism Identified: Key hypothalamic neurons become hyperactive but low-output, flattening corticosterone cycles.
- Restoring Rhythm Shrinks Tumors: Resetting the brain’s timing revived stress-hormone rhythms and increased immune-cell infiltration into tumors.
Source: CSHL
“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.”
In mice, the Borniger lab has found that breast cancer disrupts the diurnal, or day-night, rhythms of corticosterone levels. Corticosterone is the primary stress hormone in rodents. In humans, it’s cortisol. Typically, levels rise and fall naturally throughout the day. In breast cancer, the team found that tumors flatten corticosterone release, reducing quality of life and increasing mortality.
Disruptions to our own diurnal rhythms have been linked to stress responses like insomnia and anxiety—both common among cancer patients. The body depends on a feedback loop called the HPA axis to maintain healthy stress hormone levels. The hypothalamus (H), pituitary gland (P), and adrenal glands (A) work together to ensure regular day-night rhythms.
Borniger was surprised to find that in mice, breast cancer can disrupt those rhythms before tumors take hold: “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.”
When the team looked at the hypothalamus, they saw that key neurons were locked into a hyperactive, yet low-output state. Once the team stimulated these neurons to mimic the mouse’s normal day-night cycle, regular stress hormone rhythms restarted. The adjustment pushed anti-cancer immune cells into breast tumors, causing them to shrink significantly. 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.”
The team is now investigating exactly how tumors disrupt the body’s healthy rhythms. Borniger hopes their work may one day help bolster existing therapies.
“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.”
Key Questions Answered:
A: It disrupts hypothalamic neuron activity, flattening natural day-night rhythms long before tumors are physically detectable.
A: Altered rhythms can worsen stress, sleep, and immune responses, potentially contributing to poorer quality of life and lower survival.
A: In mice, yes—resetting brain-timing signals revived healthy hormone patterns and helped immune cells shrink tumors.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this cancer and neuroscience research news
Author: Samuel Diamond
Source: CSHL
Contact: Samuel Diamond – CSHL
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Aberrant hypothalamic neuronal activity blunts glucocorticoid diurnal rhythms in murine breast cancer” by Jeremy Borniger et al. Neuron
Abstract
Aberrant hypothalamic neuronal activity blunts glucocorticoid diurnal rhythms in murine breast cancer
Breast cancer patients often exhibit disrupted diurnal rhythms in circulating glucocorticoids (GCs), such as cortisol.
This disruption correlates with reduced quality of life and higher cancer mortality; however, the exact cause of this phenomenon remains unclear.
Here, we demonstrate that breast tumor-bearing mice exhibit blunted GC rhythms and a loss of diurnal rhythms in the activity of paraventricular hypothalamic neurons expressing corticotropin-releasing hormone (PVNCRH).
This change in neuronal activity is mediated by disinhibition from upstream GABAergic neurons.
Using chemogenetics to stimulate PVNCRH neurons at different times of day, we show that stimulation just before the light-to-dark transition restores normal GC rhythms, reduces tumor progression, and increases intra-tumor effector T cells (CD8+).
Our findings demonstrate that breast cancer distally regulates neurons in the hypothalamus that control the output of the hypothalamic-pituitary-adrenal (HPA) axis and provide evidence that therapeutic targeting of these neurons could mitigate tumor progression via enhancing anti-tumor immunity.
