Breast Cancer Prevention and Early Detection Laboratory


Breast cancer is the most common non-cutaneous cancer and a leading cause of cancer deaths in women. The goal of our research at the Breast Cancer Prevention and Early Detection Laboratory is to develop noninvasive and minimally invasive tools to aid in preventing and detecting breast cancer. Up to 40% of early breast cancers are missed using the current screening tools of mammography and physical examination. When a mass is felt or a mammographic abnormality detected, the patient must undergo an invasive diagnostic procedure, with its attendant risks and cosmetic alterations. Additional tools are needed to identify women with early stage disease, as well as those most likely to develop breast cancer in the future. In 1958, Dr. George Papanicolaou was the first to collect breast fluid to screen for cancer. Epidemiologic studies on thousands of women since then have confirmed that breast nipple aspiration is a safe, noninvasive method to collect breast epithelial cells, which give rise to most breast cancers, as well as secreted proteins, which are highly concentrated in the breast fluid and therefore easier to measure than those in corresponding serum. In 1994, Dr. Edward Sauter and his research team developed clinical trials using breast nipple aspiration. Since then, more than 700 women have been enrolled in these research studies. The goal is to identify markers, or indicators, of breast cancer risk. These studies have demonstrated that nipple aspirate fluid can be collected in essentially all adult women without side effects, that it can be repeated as necessary if additional samples are needed, and that markers of breast cancer risk can be identified. The markers include: Nipple aspirate cytology, which, if abnormal, is highly associated with the presence of both newly diagnosed and residual breast cancer Ploidy, which, if abnormal, is highly associated with the presence of breast cancer Prostate-specific antigen, made by the breast and inversely associated with breast cancer risk Insulin-like growth factor binding protein-3, the major binding protein of IGF-I, secreted by the breast ductal cells and directly associated with breast cancer risk. While nipple aspiration has many strengths, a weakness is the relatively low and mixed cellularity of the specimens. This low and mixed cellularity limits our ability to perform molecular studies where cell number and purity are important. Therefore, we are now performing breast ductoscopy. This minimally invasive technique allows us to view the wall of the breast duct for irregularities. An abnormal area can be sampled for diagnostic purposes or for molecular studies. The specimens are highly cellular and enriched in epithelial cells. Click to view video of ductoscopy. Breast nipple aspiration and ductoscopy, alone or in combination, provide noninvasive and minimally invasive methods to evaluate the breast for new or recurrent disease, as well as for response to a chemopreventive or chemotherapeutic agent. We have a number of ongoing clinical trials using nipple aspiration and ductoscopy. We are currently using these techniques in women: scheduled to undergo diagnostic breast surgery between the time of diagnostic biopsy and definitive surgery being treated with a chemopreventive agent previously treated with radiation for early stage breast cancer who are healthy to evaluate the effects on the breast of alternative medications such as those contained in soy The large selection provides an opportunity for a wide variety of women to enroll. In addition to our clinical trials, we have demonstrated that epithelial cells in the breast aspirate and ductoscopic specimens can be developed into primary cultures or analyzed for loss of heterozygosity or altered expression of multiple genes using cDNA and protein chips. The goal of this work is to develop a biomarker profile that is highly sensitive and specific in predicting breast cancer risk using these noninvasive and minimally invasive techniques. Top

Edward R. Sauter, MD, PhD Division of Surgical Oncology Department of Surgery University of Missouri Health Care	musurgery.org I-Net Administrator \| Network Manager 2000 © Curators of the University of Missouri-Columbia DMCA and Other Copyright information An Equal Opportunity/ADA Institution