Androgens in human breast carcinoma

Abstract

Sex steroids play important roles in the development of human breast carcinoma. Androgen receptor (AR) is expressed in a majority of breast carcinoma tissues. However, the significance of androgen actions remains largely unclear in breast carcinoma, differing from estrogen actions. Therefore, in this review, we summarized recent studies on androgens in breast carcinoma. Concentration of a potent androgen, 5alpha-dihydrotestosterone (DHT), was significantly higher in breast carcinoma tissue than in plasma, and DHT is considered to be locally produced from circulating androstenedione by 17beta-hydroxysteroid dehydrogenase type 5 and 5alpha-reductase. On the other hand, aromatase was recently reported as a negative regulator for intratumoral DHT production by possibly reducing the precursor testosterone. Androgens predominantly show antiproliferative effects in breast carcinoma cells, but association between AR status and the clinical outcome of the patient remains controversial, perhaps partly because AR status does not necessarily reflect androgenic action in breast carcinoma. Recently, molecular apocrine breast carcinoma was identified by microarray analysis. Molecular apocrine carcinoma was characterized by being estrogen receptor (ER) negative and AR positive and by being associated with increased androgen signaling and apocrine features. Therefore, androgenic actions may also be involved in apocrine features in breast carcinoma.