Mapping Molecular Alterations in Breast Cancer Using Mammary Ductoscopy.
Danh Tran-Thanh, Dong-Yu Wang, Vladimir Iakovlev, Chunjie Wang, Juan C Moreno, Scott Boerner, Naomi Miller, Bruce Youngson, Wey L Leong, Susan J Done. CHUM Hotel-Dieu, Montreal, QC, Canada; Campbell Family Institute for Breast Cancer Researcn, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; University of Toronto, ON, Canada
Background: Mammary ductoscopy is a new endoscopic technique that has the potential to allow direct visualization and sampling of tumor-containing mammary ducts. We are taking advantage this new technique to obtain epithelial cells at different intervals along these ducts. This will allow us to define a geographic map of the genetic alterations leading to malignancy in breast cancer.
Design: A series of women undergoing mastectomy for invasive breast cancer were subjected intraoperatively to mammary ductoscopy to identify the duct leading to the tumor and obtain cytology samples. Immediately after removal of the breast, a set of snap-frozen tissue samples were harvested along the identified duct as well as from the tumor itself. Nucleic acids were extracted from all cytological and microdissected tissue samples and subjected to array CGH and gene expression array profiling.
Results: Twenty-one patients undergoing mastectomy have been recruited in our study. Array CGH and gene expression data showed an increasing number of genetic alterations in epithelial ductal cells going from the nipple towards the tumor. Furthermore, in a small number of patients, genetic abnormalities similar those found in tumors can be identified in histologically normal ducts sampled close to the tumor. These include alterations to chromosomes 1q12-21, 8q21-24, 17q12-21 and 20q13.2, and might represent the earliest molecular changes leading to breast cancer. In addition, pathway analysis using gene expression data obtained from different regions of the affected duct demonstrated that certain pathways, notably the E2F1 and β-catenin pathways, were altered early on during tumorigenesis. On the other hand, activation of pathways such as PI3K or IFN-γ seemed to be occurring later.
Conclusions: Mammary ductoscopy is a useful technique for mapping molecular alterations in breast cancer patients. Using microarray data, we have identified chromosomal regions that might represent the earliest changes and pathways that seem to be activated early on during breast cancer development. Identification of some of the earliest events in tumourigenesis may result in new strategies to block the development and progression of breast cancer.
Monday, February 28, 2011 1:00 PM
Poster Session II # 264, Monday Afternoon