Systematic review identifies stress-induced biological activators in oncology

Anxiety is a constant companion in the oncologist’s office. It appears at the time of diagnosis, increases with each stage of treatment, and often does not subside even after the official end of treatment. It accompanies treatment decisions, waiting for test results, fear of relapse and changes in daily functioning. Studies show that chronic stress can trigger biological processes that promote disease progression and weaken the body’s defenses.

This perspective is presented in a systematic review prepared by researchers from the Medical University of Wroclaw, published in 2026 in International Journal of Molecular Sciences. The authors analyzed data for four cancers—breast, prostate, pancreatic, and ovarian—arranging them according to five-year survival rates.

What exactly is chronic stress?

From a biological perspective, chronic stress is a long-term strain on the body’s adaptive capacity. It is not a one-time reaction to a difficult event, but a situation in which the systems responsible for dealing with threats remain active for weeks or months.

In oncology stress is multidimensional. It includes not only stress and grief, but also social, professional, family and existential factors. For many patients, it means redefining their life plans, social roles and sense of control over their bodies.

The authors of the review describe the mechanisms linking chronic stress to the course of cancer in a way that can be reduced to three related stages:

1. Hormonal alarm

Chronic stress leads to persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. In practice, this means a long-term increase in cortisol, adrenaline and noradrenaline levels.

As a co-author of the review, Katarzyna Herbetko emphasizes: -The body functions as if it is constantly in a state of danger. This is associated with increased inflammation and immunosuppression, which can promote tumor progression and weaken response to treatment.

1. Immunity and inflammation

Stress hormones affect the immune system. Prolonged exposure to cortisol and catecholamines can weaken immune surveillance and shift the balance toward chronic low-grade inflammation. This is an environment in which cancer cells can more easily survive, proliferate and evade control mechanisms.

1. Volume environment

At the tissue level, chronic stress can affect angiogenesis, cancer cell migration, and processes associated with treatment resistance.

However, the authors consistently point out a key caveat: these mechanisms are biologically consistent with current knowledge, but in clinical trials, it is very difficult to disentangle the impact of stress from disease progression, treatment intensity, and other clinical factors.

Not all cancers are the same

One of the key findings of the review is that chronic stress does not affect all cancers equally. Its biological and clinical significance depends both on the type of disease and on its prognosis.

In cancers with better survival rates, such as breast and prostate cancer, anxiety most often takes the form of chronic uncertainty. Patients live with the disease for a long time, struggling with the fear of relapse, the side effects of treatment and permanent changes in their quality of life. In this context, the biological role of adrenergic and glucocorticoid signaling comes to the fore, which, in preclinical studies, is related, among other things, to metastasis and response to treatment. This is not to say that stress “undermines healing,” but rather that, in some patients, it may be an additional biological factor contributing to disease progression.

A different picture emerges in cancers with a worse prognosis, such as pancreatic and ovarian cancer. In this group, psychological distress and depression are more common and usually more severe. Importantly, psychological symptoms may sometimes precede a cancer diagnosis, suggesting the involvement of biological mechanisms rather than simply an emotional reaction to the diagnosis. At the biological level, inflammatory and cytokine mechanisms predominate, including elevated IL-6 levels and significant systemic stress.

Psychological distress is not just an emotion, but a factor that can contribute to the physiological overload of the body and deplete the reserves necessary for the healing process.”

Katarzyna Herbetko, Faculty of Medicine, Medical University of Wroclaw

Psychotherapy – more than just talking

The review authors emphasize that psychotherapy in oncology is not just about emotional support. Evidence shows that psychological interventions can:

• reduction of anxiety and depression,
• improving quality of life,
• affect markers of stress and inflammation, such as cortisol levels and selected cytokines.

At the same time, researchers remain cautious in their interpretation.

“There is no simple correlation: psychotherapy = longer survival. We see real, measurable biological changes, but the current state of knowledge does not allow clear conclusions about mortality,” added Katarzyna Herbetko.

It is worth noting that the effect of psychological treatment can weaken after its completion, which indicates the need for long-term and not episodic support.

Conclusions and recommendations

The authors clearly point out the limitations of the available data:

• heterogeneous stress measurement methods,
• lack of meta-analyses that allow precise quantitative conclusions,
• difficulty separating stress as a biological factor from stress as a consequence of serious illness and treatment.

The most important message of the review is clear: chronic stress is not the patient’s fault. Rather, it is a factor associated with measurable biological processes that, such as pain, malnutrition, or sleep disturbances, can and should be addressed clinically.

The authors suggest:

• the systematic inclusion of psycho-oncology in the standard of care,
• regular risk check and quick help,
• support for partners and carers,
• development of digital interventions (eHealth) and strategies to sustain treatment outcomes.

As Katarzyna Herbetko summarized, “Psycho-oncology cannot be additive. Chronic stress should be treated as a modifiable risk factor in oncology, analyzed in the context of complex biological, psychological and environmental interactions.”