Molecular methods will hold promise for the detection of fewer numbers of cells than conventional histological examination. The molecular changes in cancer include epigenetic alterations, such as the abnormal methylation of promoter regions of CpG islands. Molecular techniques based on the sensitive detection of abnormal methylation now exist and hold promise as one such molecular method for detection of tumor cells. Breast cancer, like many other malignancies, has recently been shown to have abnormal methylation of many genes, including some tumor suppressor genes. These changes can then serve as the basis for a molecular detection strategy. The management of breast cancer patients can benefit form more accurate methods of determining risk of disease recurrence following surgical resection. While the majority of women with histologically negative lymph nodes will be cured by local therapy alone, approximately, twenty-five to thirty percent of these patients will go on to recur and die of their disease within ten years of the time diagnosis. A molecular means to more accurately predict recurrence in this group would be desirable. Early detection of breast cancer results in improvements in mortality from the detection of early, more readily curable disease. However, 10-15% of breast cancers are not detected by mammography. An improved method of detection might improve the survival of patients whose tumors are not detectable by mammography.
The specific aims are: 1) To develop and optimize tumor specific DNA methylation changes as a molecular marked in breast cancer and validate this approach in the molecular staging of breast cancer. 2) To use the tissues obtained in a prospective ongoing trial of sentinel lymph node biopsy technology to subdivide the node negative group of patients into group of patients into groups with differing prognoses based on molecular evidence of methylated alleles representing nodal metastasis. 3) To examine the feasibility and utility of the detection of methylated alleles in nipple aspirate fluids (NAF) and ductal lavage (DL) for the early detection of breast cancer.
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