As breast cancer progresses, tumor cell heterogeneity increases, metastatic colonization increases, and survival time decreases. At the same time, a new study from the University of Basel indicates, the activation of glucocorticoid receptors (GRs) in metastases increases. The activation of GRs, which mediate the effects of stress hormones, does not appear to be coincidental. Indeed, it may explain why stress has been thought to contribute to cancer progression.

By implicating GRs in the spread of breast cancer, the new study raises concerns about the use of glucocorticoids to treat the side effects of chemotherapy. In fact, the University of Basel scientists, led by Mohamed Bentires-Alj, professor of experimental surgical oncology, showed that in mice with metastatic cells, the efficacy of the chemotherapy drug paclitaxel was decreased when administered in combination with dexamethasone, a synthetic derivative of the stress hormone cortisol.

Details from the study appeared March 13 in the journal Nature, in an article entitled, “Glucocorticoids promote breast cancer metastasis.” For example, the article describes how the University of Basel scientists used transcriptional profiling of tumors and matched metastases in patient-derived xenograft models in mice.

This comprehensive evaluation of gene expression allowed the scientists to explore cancer cell heterogeneity, which increases during cancer progression and complicates treatment. It also enabled the scientists to identify cancer-site-specific phenotypes and increased GR activity in distant metastases.

“Our transcriptomics, proteomics, and phospho-proteomics studies implicate the glucocorticoid receptor in the activation of multiple processes in metastasis and in the increased expression of kinase ROR1, both of which correlate with reduced survival,” the article’s authors wrote. “The ablation of ROR1 reduced metastatic outgrowth and prolonged survival in preclinical models.”

These findings suggest that caution should be taken when prescribing glucocorticoid hormones to patients with breast cancer. The study also suggests that GR inhibition may be beneficial for patients and could lead to the development of new therapies to combat breast cancer metastasis.

“Tumor heterogeneity is a serious hurdle for therapy. These findings highlight the importance of stress management in patients—and especially those with triple-negative breast cancer,” stated Bentires-Alj. “Moderate exercise and relaxation techniques have been shown to correlate with enhanced quality of life and greater survival in patients.”

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