IMMUNOASSAYS SPECIFIC FOR ESTROGEN RECEPTOR ISOFORMS

BREAST CANCER IS THE PRINCIPAL CAUSE OF CANCER DEATH AMONG WOMEN IN THE UNITED STATES AND WESTERN EUROPE. IDENTIFICATION OF BREAST TUMORS THAT ARE CANDIDATES FOR ENDOCRINE THERAPY (I.E., TAMOXIFEN) HAS BEEN BASED UPON DETECTION OF ESTROGEN RECEPTORS (ER) AND PROGESTERONE RECEPTORS (PR) IN A BIOPSY. ER(-) TUMORS ONLY RARELY RESPOND TO TAMOXIFEN THERAPY, WHEREAS APPROXIMATELY HALF OF THE TUMORS SHOWN TO BE ER(+) BY PRESENTLY AVAILABLE ASSAYS RESPOND TO SUCH THERAPY. TUMORS THAT ARE BOTH ER(+) AND PR(+) HAVE AN EVEN GREATER LIKELIHOOD OF RESPONDING TO TAMOXIFEN, BUT 20 TO 25 PERCENT 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 WHY THE PRESENTLY AVAILABLEASSAYS 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. THEAVAILABILITY OF SUCH ASSAYS SHOULD ALLOW FOR BETTER CHARACTERIZATION OF THESE BIOPSIES, SHOULD PROVIDE A MORE EFFICIENT PREDICTOR OF WHICH TUMORS ARE MOST LIKELY TO RESPOND TO ENDOCRINE THERAPY, AND SHOULD BE A MORE ACCURATE PROGNOSTIC INDICATOR OF THE SUBSEQUENT CLINICAL COURSE OF THE DISEASE.