Cortisol and Breast Cancer: A review of clinical and molecular evidence

Abstract

Breast cancer (BC) is a commonly diagnosed cancer amongst women and the second leading cause of cancer deaths in the world. BC has created huge challenges to healthcare providers regarding the identification of main risk factors and how they contribute to the development of the disease. Several studies suggest that biological risk factors such as duration of breast feeding, age at menarche, menopausal status and the use of contraceptive pills have contributed to the increase of BC diagnoses. Moreover, psychological factors such as depression, stress and negative lifestyles are gaining more attention as a major contributor to this type of cancer. The role of psychological stress regarding BC has been widely demonstrated in the literature across several fields including but not exclusive to epidemiology, physiology, and molecular biology which all show a clear relationship between intracellular stress signaling and protumorigenic pathways within breast cells. Cortisol is primary stress hormone of the human body and a growing body of research both clinically and molecularly are revealing a positive correlation of high cortisol levels and the progression of BC. This review attempts to establish and highlight how cortisol levels impact breast cancer development and progression.

Association of High Dietary Acid Load With the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies

“…Cortisol is a stress hormone that controls numerous processes throughout the body, such as metabolism and performance of the immune system. A growing body of evidence is suggesting a positive relationship between high cortisol levels and the progression of cancer ( 48 – 50 ). High cortisol concentrations adversely suppress the immune system and decrease its sufficiency in eliminating mutated cells ( 48 ).…”

“…A growing body of evidence is suggesting a positive relationship between high cortisol levels and the progression of cancer ( 48 – 50 ). High cortisol concentrations adversely suppress the immune system and decrease its sufficiency in eliminating mutated cells ( 48 ). In addition, higher cortisol concentrations may contribute to the development of cancer by increasing DNA damage and apoptosis suppression ( 48 ) ( Figure 4 ).…”

Meta-Analysis of Microdissected Breast Tumors Reveals Genes Regulated in the Stroma but Hidden in Bulk Analysis

“…The latter is the enzyme that converts cortisol in cortisone, which is down-regulated in tumor stroma and correlates with a lower grade. Its decrease across tumor progression might be responsible for high cortisol levels, which have been associated with higher severity and mortality [120]. To our knowledge, this is the first time that such a relationship has been detected in the stroma.…”

Meta-Analysis of Microdissected Breast Tumors Reveals Genes Regulated in the Stroma but Hidden in Bulk Analysis

“…Among regulated genes we find UPB1 and HSD11B2, the enzyme that converts cortisol in cortisone, which is down-regulated in tumor stroma and correlated with lower grade. Its decrease across tumor progression might be responsible for high cortisol levels, which have been associated with higher severity and mortality [118]. UPB1 codes for the last enzyme in the pyrimidine degradation pathway, and its down-regulation might lead to dihydropyrimidine accumulation, linked with EMT [119].…”