ONCOGENE MARKERS AND CANCER RISK IN BENIGN BREAST CANCER

THIS RESEARCH WILL DEVELOP AN ASSAY TO PREDICT WHICH PATIENTS ARE AT HIGH RISK TO DEVELOP INVASIVE CANCER AT THE TIME OF BIOPSY-PROVEN BENIGN BREAST DISEASE. THE APPROACH WILL QUANTITATE CELLS IN BENIGN BREAST DISEASE TISSUE THAT HAVE ACQUIRED AUTONOMOUS PHENOTYPES WITH RESPECT TO HORMONES AND GROWTH FACTORS THAT NORMALLY EVOKE AN ORDERLY PATTERN OF GROWTH TO TERMINAL DIFFERENTIATION. SUCH AN APPROACH WILL IDENTIFY THE PRESENCE OF OCCULT AGGRESSIVE CANCER CLONES AND DETERMINE IF A HIGH DEGREE OF IMMORTALITY HAS BEEN ACQUIRED BY THE BENIGN LINEAGE. PHASE I RESEARCH WILL DETERMINE IF IT IS POSSIBLE TO DETECT BY IN SITU HYBRIDIZATION DIFFERENCES IN THE CELLULAR MRNA LEVEL OF EGF RECEPTOR (ERB-B), THYROXIN RECEPTOR (ERB-A), INSULIN, IGF-1 (SOMMA-TOMEDIN), ESTROGEN, PROGESTERONE, GLUCOCORTICOID OR PROLACTIN RECEPTOR, HER2/NEU, C-MYC,C-FOS, AND C-HA-RAS GENES SPECIFICALLY IN BENIGN BREAST DISEASE FROM PATIENTS WITH THE HIGHEST CANCER RISK (THOSE WITH INVASIVE CANCER INVOLVEMENT). IF THIS APPROACH IS VALID, IT IS EXPECTED TO SEE ONE OR MORE RECEPTORS OR C-ONC MRNA DIFFERENTIALLY OVER- OR UNDEREXPRESSED SPECIFICALLY IN ATYPICAL PROLIFERATIVE HYPERPLASIAS AND THE DIFFERENTIAL EXPRESSION SELECTED IN IN SITU LESIONS AND THE INVASIVE CANCERS FROM THE SAME PATIENTS. IN PHASE II, THE VALIDATED PROBE(S) WILL BE USED IN A STUDY OF MORE THAN 1,000 CANCER PATIENTS.