Androgen Receptor Expression Is Usually Maintained in Initial Surgically-Resected Breast Cancer Metastases But Often Lost in End-stage Metastases Found at Autopsy

摘要

Androgen receptor (AR) is expressed in approximately 70% of primary breast carcinomas and is a promising therapeutic target for metastatic breast carcinoma. Here, we examine AR expression in a population of initial surgically-resected metastases and a separate cohort of end-stage metastases harvested at autopsy compared to their matched primary breast carcinomas. Tissue microarrays of matched primary and metastatic breast carcinomas were labeled by immunohistochemistry for AR, ER, PR, and Her2 and classified into the following previously-described categories: luminal (ER/PR+/Her2−), triple negative (ER/PR/Her2−), Her2 (ER/PR−/Her2+), and luminal loss (ER/PR loss from primary to metastasis). In the cohort of surgically-resected metastases (n=16), AR was expressed in 12/16 primaries and maintained in 11/12 corresponding metastases. Of these, 36% showed stronger AR labeling in the metastases and none showed a decrease. In the cohort of metastases harvested at autopsy (n=16), AR was expressed in 11/16 primary carcinomas and maintained in only 5/11 corresponding metastases. Of these, none showed increased AR and 80% showed decreased AR labeling. AR expression is overwhelmingly concordant between matched primary and metastatic breast carcinomas at initial presentation. These findings validate AR as a therapeutic target in metastatic breast carcinoma and suggest that AR may need to be reevaluated in metastases even if the primary is negative. However, similar to ER/PR, AR expression is often decreased with a trend towards complete loss in end-stage metastases, suggesting a shift of AR expression between initial and end-stage metastases. This suggests an opportunity for targeted anti-androgen therapy at an earlier stage of disease progression.