Divergent features of ER isoforms in triple negative breast cancer: progress and implications for further research

Estrogen receptor beta (ER beta) was discovered more than 20 years ago. However, the extent and role of ER beta expression in breast cancer remain controversial, especially in the context of triple-negative breast cancer (TNBC). ER beta exists as multiple isoforms, and a series of studies has revealed an inconsistent role of ER beta isoforms in TNBC. Our recent results demonstrated contrasting functions of ER beta 1 and ER beta 2/beta 5 in TNBC. Additional research should be conducted to explore the functions of individual ER beta isoforms and develop targeted drugs according to the relevant mechanisms. Consequently, a systematic review of ER beta isoforms is necessary. In this review, we overview the structure of ER beta isoforms and detail what is known about the function of ER beta isoforms in normal mammary tissue and breast cancer. Moreover, this review highlights the divergent features of ER beta isoforms in TNBC. This review also provides insights into the implications of targeting ER beta isoforms for clinical treatment. In conclusion, this review provides a framework delineating the roles and mechanisms of different ER beta isoforms in TNBC and sheds light on future directions for basic and clinical research.