The glucocorticoid receptor signalling in breast cancer

•  Introduction ‐  Glucocorticoid receptor structure and mechanism of action ‐  Cell survival and apoptosis ‐  Growth factor signalling ‐  Oncogenes ‐  Tumour suppressor genes ‐  Metastasis suppressor genes ‐  Transcription factors ‐  Signalling pathways cross‐talk ‐  Cross‐talk with other steroid receptor signalling ‐  Cytokines ‐  11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2):conversion of cortisol to cortisone ‐  GR expression in human breast tissues ‐  Non‐genomic GC effects•  Concluding remarksAbstract Glucocorticoids (GCs) are provided as co‐medication with chemotherapy in breast cancer, albeit several lines of evidence indicate that their use may have diverse effects and in fact may inhibit chemosensitivity. The molecular basis of GC‐induced resistance to chemotherapy in breast cancer remains poorly defined. Recent researchers, in an attempt to clarify some aspects of the underlying pathways, provide convincing evidence that GCs induce effects that are dependent upon the glucocorticoid‐receptor (GR)‐mediated transcriptional regulation of specific genes known to play key roles in cellular/tissue functions, including growth, apoptosis, differentiation, metastasis and cell survival. In this review, we focus on how GC‐induced chemoresistance in breast cancer is mediated by the GR, unravelling the molecular interplay of GR signalling with other signalling cascades prevalent in breast cancer. We also include a detailed description of GR structure and function, summarizing data gained during recent years into the mechanism(s) of the cross‐talk between the GR and other signalling cascades and secondary messengers, via which GCs exert their pleiotropic effects.