The interplay of endocrine therapy, steroid pathways and therapeutic resistance: Importance of androgen in breast carcinoma

A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified. In breast carcinoma tissues, not only ER but androgen receptor (AR) is frequently expressed, suggesting pivotal roles of androgens in the progress of breast carcinomas. Growing interest on androgen action as possible therapeutic target has been taken, but androgen action seems quite complicated in breast carcinomas and inconsistent findings has been also proposed. In this review, we will summarize recent studies regarding intratumoral androgen production and its regulation as well as distinct subset of breast carcinomas characterized by activated AR signaling and recent clinical trial targeting AR in the patients with either ER-positive and ER-negative breast carcinomas.