Cytoplasmic Mineralocorticoid Receptor Expression Predicts Dismal Local Relapse-free Survival in Non-triple-negative Breast Cancer

Abstract

Background/Aim: The aim of the study was to investigate the prognostic role of androgen receptor (AR), mineralocorticoid receptor (MR) and glucocorticoid receptor β (GRβ) expression in HER-2 negative breast cancer patients. Materials and Methods: The study population (n=152) was enriched with triple-negative breast cancers (TNBC) (n=96; 63.2%). The median follow-up time was 100 months. AR, MR and GRβ immunocytochemical staining was compared with that of epithelial-mesenchymal transition (EMT) markers (vimentin, SIP1, ZEB1). Results: High expression of cytoplasmic MR was associated with dismal local relapse-free survival (RR=13.923; 95%CI=1.071-181.045; p=0.044) in tumours with non-TNBC phenotype. AR and GRβ were more frequently expressed in ER+/PR+/HER2-tumours, while cytoplasmic MR was more often expressed in TNBC tumours (for all, p<0.0005). GRβ and AR were associated with decreased vimentin expression (p<0.005), indicating their association with attenuated EMT. Conclusion: Cytoplasmic MR expression is a strong predictor of local recurrence in non-metastatic breast cancer patients with non-TNBC tumour phenotype.

Genome-wide crosstalk between steroid receptors in breast and prostate cancers

“…However, some investigators have explored the MR’s potential role in both cancers. Both glucocorticoids and mineralocorticoids, together with PR, can decrease BCa cell proliferation ( Leo et al 2004 ), and a high cytoplasmic expression of MR has been associated with a poor survival of ER+/PR+/HER2- BCa patients ( Jääskeläinen et al 2019 ). In PCa, abiraterone treatment can result in excess of aldosterone and its precursors, which increases the risk for hypertension and cardiovascular diseases ( Pia et al 2013 , Narayanan et al 2016 ).…”

Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development

“…Several isoforms of GR have been described to this day: GRα (the ‘standard’ form), GRβ—Which is present in the nucleus (however, some studies revealed its significant presence only in the cytoplasm [ 175 ]), has no LBD [ 169 ], exhibits constant activity and suppresses the effects of GRα. Apart from that, GRβ possesses other specific DNA targets and is responsible for glucocorticoid resistance.…”

“…In turn, GRα is repressed by Akt1, which phosphorylates its S134 residue [ 170 ] GRβ is preferentially expressed with AR in breast tumors and was revealed to be present in 92.1% of specimens, typically in triple-negative tumors. It has been shown that its presence is correlated with less vimentin expression in breast tumors in general and in non-triple-negative breast cancers and with lesser proliferation in breast cancers in general [ 175 ].…”

“…MR can heterodimerize with other steroid receptors, especially AR and GR [ 187 ]. The exertion of PR-like effects by the MR is suspected [ 175 ]. MR was shown to be expressed in larger amounts in presence of PR [ 175 ].…”

“…The exertion of PR-like effects by the MR is suspected [ 175 ]. MR was shown to be expressed in larger amounts in presence of PR [ 175 ]. However, according to some sources, dexamethasone and deoxycorticosterone are weak agonists of MR in the absence of aldosterone, in its presence de facto working as antagonists by suppressing its N/C-interaction and consequent conformation change.…”