description) Improvements in screening techniques have made significant contributions to the early detection of breast cancer. At present 10-20%of newly diagnosed breast cancers in screened populations are classified as in-situ lesions. Conservative treatment with mastectomy provides essentially a 100% cure rate while breast conserving techniques have been associated with up to 30% risk of recurrence, oftentimes in the form of invasive cancer. Preliminary evidence suggests, however, that some subsets of in-situ cases may be good candidates for breast conserving techniques although the data are extremely sparse; consequently, it is imperative that this information be gathered in a timely fashion. The proposed study will identify in-situ breast lesions that have an increased probability of progressing to invasive carcinoma. Approximately 250 in-situ breast tumor specimens excised from female breast cancer patients from 1980 to present at Yale-New Haven Hospital and stored in the form of paraffin-embedded tumor blocks, will be tested for amplification of the putative chromosome 17 oncogenes, p53 and c-erbB-2, using the methods of immunohistochemistry. The joint distribution of p53 and c-erbB-2 over-expression will be examined by tumor size and grade to examine the correlation between timing of these two molecular events. Clinical information such as estrogen receptor status and family history of breast cancer will be collected from medical records and examined according to oncogene expression. Followup data will be gathered for these cases using the Yale-New Haven Hospital and Connecticut Tumor Registries to determine whether over expression of either of these genes is associated with reduced disease-free or overall survival. Tumor specimens from women who suffer a recurrence will also be collected and tested for the presence of p53 c-erbB-2 over-expression. The identification tumors having a high probability of progression to invasive carcinoma using standardly excised biopsy material would provide physicians with a powerful clinical tool, enabling in-situ patients (estimated to include up to 20,000 women in the United States in 1992 alone) to choose a less physically disfiguring treatment scheme without compromising the probability of disease-free or overall survival.
