Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

摘要

Women who are carriers of inherited germline mutations have an 85% lifetime risk of developing breast cancer. BRCA1 carriers are more likely to develop tumors at an earlier age that are estrogen receptor negative, therefore they cannot benefit from antiestrogen chemopreventive treatments. Because currently it is not possible to predict who will actually develop breast cancer, we have designed studies using molecular approaches for identifying the " high risk" genomic signature of the cytological normal breast epithelium of women at high risk for breast cancer. This signature will serve as an intermediate biomarker for evaluating the response of the breast to novel chemopreventive agents. We performed cDNA microarray analysis of pure epithelial cell populations obtained by laser capture microdissection (LCM) from cytological smears of the normal human breast epithelial cell line MCF- 10F. Our observations confirmed the usefulness of combining LCM and cytospin preparations for obtaining pure cell populations for RNA extraction, and of PCR RNA amplification for cDNA microarray analysis and quantification of gene expression level by real time RT-PCR. These studies will lead to fruitful results through genomic hierarchical cluster analysis and Bioinformatics for patient risk assessment and for evaluating the responsiveness of the breast epithelium to chemopreventive agents.