Scientists at Cold Spring Harbor Laboratory have found that breast cancer quickly disrupts the brain's internal clock in mice, flattening daily stress hormone cycles and impairing immune responses. Remarkably, restoring these rhythms in specific brain neurons shrank tumors without any drugs. The discovery highlights how early physiological imbalances may worsen cancer outcomes.
Researchers led by Jeremy Borniger, an assistant professor at Cold Spring Harbor Laboratory, investigated how breast cancer affects the brain's regulation of stress and immunity. In mouse models, tumors interfered with diurnal rhythms—the natural day-night cycles of stress hormones. Normally, corticosterone levels in mice (equivalent to cortisol in humans) rise and fall predictably. However, breast tumors caused these levels to remain unnaturally flat, even before the tumors were detectable by touch.
This disruption emerged rapidly: within three days of cancer induction, the rhythm was blunted by 40 to 50 percent. Borniger noted, "Even before the tumors were palpable, we see about a 40 or 50% blunting of this corticosterone rhythm." The irregularity stems from the hypothalamic-pituitary-adrenal (HPA) axis, where hypothalamic neurons became hyperactive yet produced weak signals, throwing off the feedback loop that governs stress, sleep, and immune function.
Such imbalances are linked to common cancer symptoms like anxiety and insomnia, and in the mice, they correlated with reduced quality of life and higher mortality. The team then tested an intervention: stimulating these neurons to mimic normal day-night patterns. This reset normalized hormone cycles, prompting immune cells to infiltrate tumors and significantly reducing their size.
Borniger explained the timing's importance: "Enforcing this rhythm at the right time of day increased the immune system's ability to kill the cancer... If we do the same stimulation at the wrong time of day, it no longer has this effect." Notably, no anti-cancer drugs were used; the focus was on physiological health. The findings, published in Neuron in 2025, suggest enhancing body rhythms could complement treatments, potentially reducing therapy toxicity. Further research aims to uncover how tumors initially disrupt these cycles.
