There are many factors that are believed to contribute to cancer growth. Stress is one of them. But stress is subjective and difficult to measure. So far, studies that have established the relationship between stress and cancer have relied on empirical data. An exact scientific proof remained unresolved. A major challenge in the research and treatment of metastatic breast cancer is tumor heterogeneity. In the course of the disease, the tumor becomes more diverse. Thus, the growing differences between the individual cancer cells can lead to insufficient therapeutic success. The underlying mechanisms of this phenomenon are still unknown.

Research based on mouse cancer model

Researchers from the University of Basel and the University Hospital of Basel recently uncovered the molecular mechanisms that link breast cancer metastases with increased stress hormones. For their studies, the scientists around Prof. Mohamed Bentires-Alj investigated the form of the so-called triple negative breast cancer. It is a particularly aggressive type of cancer which is named after the receptors it does not have – the estrogen receptor, progesterone receptor or HER-2 receptor – which are used to divide the surface of cancer cells. The triple negative cancer is resistant to standard therapies and offers patients fewer treatment options.

The scientists carried out their research using a mouse cancer model. In order to investigate the heterogeneity between tumors and metastases, they investigated the activity of genes. They found that metastases have increased activity in the so-called glucocorticoid receptors (GR). These receptors bind stress hormones such as cortisol.

Mice with metastases had higher concentrations of stress hormones than mice without metastases. The study shows that increased stress hormone levels activate GR. This, in turn, leads to increased colonization and heterogeneity of cancer cells. This ultimately leads to a shortened lifespan.

New therapies conceivable

The GR also bind synthetic derivatives of cortisol. These include, for example, the anti-inflammatory dexamethasone, which is often used to alleviate the side effects of chemotherapy. The research results showed that dexamethasone can impair the efficacy of the drug paclitaxel, which is widely used in chemotherapy.

The results of the Basel research group indicate that caution is advised when prescribing glucocorticoid hormones to breast cancer patients. The study also makes it clear that blocking GR can be beneficial. It could also lead to the development of new therapies to combat breast cancer metastasis.

„Tumor heterogeneity is a major obstacle in the treatment…“

…stresses Prof. Bentires-Alj. And he continues: “The importance of stress management cannot be overemphasised – especially in patients with triple negative breast cancer”. He therefore recommends moderate exercise training and relaxation techniques for affected patients. Not only according to Bentires-Alj this is demonstrably connected with an improved quality of life and increased life expectancy.

The study was recently published in the International Journal of Science Nature. Prof. Bentires-Alj and Prof. Walter Paul Weber, chief physician of the Department of Breast Surgery at the University Hospital Basel, are the founders of the Brustkonsortiums Basel.

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