Breast cancer is the principal cause of cancer death among women in the United States and Western Europe. Identification of patients who are candidates for endocrine therapy (i.e. tamoxifen treatment) has been based upon detection of estrogen receptors (ER) and progestin receptors (PR) in the breast tumor biopsy. Patients with ER- tumors only rarely respond to tamoxifen, whereas approximately half of the tumors shown to be ER+ by presently available assays respond to such therapy. Patients with breast tumors which are both ER- and PR+ have an even greater likelihood of responding to tamoxifen, but 20 to 25% of those tumors are still unresponsive to that therapeutic strategy. Presently available tests can only detect a certain subset of the many isoforms of ER present in breast tissue. 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 ascertaining ER profiles in breast carcinomas. In Phase I, several monoclonal antibodies were developed which show varying patterns of isoform specificity. In Phase II, this panel of antibodies will be expanded, characterized and utilized to develop isoform specific immunoassays. The availability of assays which distinguish among different ER isoforms should provide a more effective prognostic indicator of which tumors are most likely to respond to endocrine therapy, and should be a more accurate predictor of the subsequent clinical course of the disease.
