ROLE OF THE ANDROGEN RECEPTOR IN HUMAN BREAST-CANCER

Although the androgen receptor (AR)(3) is often co-expressed with the estrogen receptor (ER) and progesterone receptor (PR) in human breast tumors, its role in breast cancer is poorly understood. Specific growt h stimulatory and inhibitory actions of androgens have been described in human breast cancer cell lines. The mechanisms by which androgens e xert these contrasting growth effects are unknown. A commonly utilized second line therapy for the treatment of advanced breast cancer is hi gh dose medroxyprogesterone acetate (MPA). Although MPA, a synthetic p rogestin, was thought to act exclusively through the PR, the androgeni c side-effects observed in women taking MPA suggest that its action ma y also be mediated in part by the AR. In support of this hypothesis, t he level of AR measured by radioligand binding in primary breast tumor s was correlated with the duration of response to MPA treatment follow ing failure of tamoxifen therapy. Recent data suggest that the presenc e of structurally altered AR in breast cancers may account for unrespo nsiveness to MPA in some of these cases. Further studies are warranted to determine the role of AR mediated pathways in regulating breast tu mor growth. In particular, identification of androgen-regulated genes may lead to new possibilities for the hormonal treatment of breast can cer.