Breast cancer is the principal cause of cancer death among women in the United States and Western Europe. Identification of breast tumors which are candidates for endocrine therapy (i.e. tamoxifen) has been based upon detection of estrogen receptors (ER) and progesterone receptors (PR) in the biopsy. ER tumors only rarely respond to tamoxifen therapy, whereas approximately half of the tumors shown to by ER+ by presently available assays response to such therapy. Tumors which are both ER+ and PR+ have an even greater likelihood of responding to tamoxifen, but 20 to 25% of those tumors still are unresponsive. The fact that presently available assays can only detect a certain subset of the many isoforms of ER present in breast tissue may be one of the reasons that the presently available assays are not better predictors of tamoxifen responsiveness. It is the goal of this project to generate monoclonal antibodies specific for these various isoforms, and to subsequently utilize these antibodies to develop isoform specific immunoassays for specific ER isoforms.