I 1 State of the Science and the Intraductal Approach for Breast Cancer

Researchers are using the intraductal approach to advance breast cancer risk assessment, prevention, diagnosis, and treatment. Procedures and technologies that can access and interrogate the ductal-alveolar systems include nipple aspiration, ductal lavage and ductoscopy. Ductoscopic papillectomy, ductoscopic margin evaluation, and intraductal therapy are considered promising investigational and innovative treatments. These techniques are used to explore the biology of the normal breast; collect and analyze breast fluid and cells to identify biomarkers that can be used in breast cancer detection and risk assessment; and to identify new ways to find and administer therapeutic and/ or preventive agents to the breast tissue. This report summarizes the latest research findings in these areas, presented at The 6 International Symposium on the Intraductal Approach to Breast Cancer in 2009. Introduction: The human breast is composed of multiple ductal lobular systems that each open onto the surface of the nipple. These ductal systems arborize into ductal trees with associated lobules and are lined with epithelial cells, where most breast cancers are thought to originate. The application of suction to the nipple openings (nipple aspiration) and ductal lavage are used to collect fluid and exfoliated cells from the breast ducts. Many substances associated with the growth, development, and tumorigeneses of the breast have been detected in breast fluids. Cytological techniques have shown that breast cancer-associated abnormalities can be found in these cells [1–6]. In addition, the production and cytological properties of nipple aspirate fluid are associated with breast cancer risk, with long-term follow-up of women undergoing nipple aspiration having shown that breast cancer risk is two to five times greater in women diagnosed with cytologic atypia than it is for women who do not yield fluid [7]. The first International Intraductal Symposium was held in 1999. A biennial event, the Symposium includes discussions and presentations on the anatomy and physiology of the normal and diseased breast, advances in intraductal technologies, findings from genetic, epigenetic, and proteomic analyses of intraductal fluid, and the latest translational research on intraductal approaches to breast cancer risk assessment, diagnoses, and treatment. The 6 International Symposium on the Intraductal Approach to Breast Cancer, sponsored by the Dr. Susan Love Research Foundation and held in Santa Monica, California, on 19–21 February 2009, was attended by more than 100 delegates from 14 countries, including clinicians, epidemiologists, pathologists, basic scientists, translational investigators, and breast cancer advocates. The program included talks by 34 invited speakers and 16 pilot grant applicants in sessions that addressed the etiology of breast cancer; biomarkers of risk in nipple aspirate fluid and ductal lavage; anatomy, ductoscopy, and breast imaging; and intraductal therapy. Delegates also had the opportunity to attend demonstrations of ductoscopy, sonoductography, and nipple aspirate fluid collection on live volunteers. Minisymposium on a Novel Etiology for Breast Cancer: Inflammation: The first session’s speakers discussed the role that inflammation, nipple aspirate fluid and macrophages may play in breast cancer development. Lisa Coussens (University of California, San Francisco, USA) discussed her research with an MMTV-PyMT mouse model of mammary carcinogenesis that revealed a tumor-promoting role for TH2-CD4 T effector cells. These novel findings suggest the immune system modulates the early onset of cancer development in specific organs, and confirmed epidemiological studies showing that increased macrophage presence correlates with higher tumor grade and decreased survival. Eliminating the T effector cells did not regulate primary disease, and also made it more likely that the cancer would metastasize to the lung, behavior that appeared to be regulated by macrophages. These findings could one day translate into an immune signature that is an independent predictor of recurrence risk, while identifying the pro-tumor mechanisms could lead to new cancer treatments. Premalignant cell damage in the breast duct lining signals a biochemical cascade that delivers inflammatory proteins to the cell site. Chandice Covington (Texas Tech University Health Services Center, Lubbock, TX, USA) discussed one of these proteins, C-Reactive. CRP is associated with cancer risk, and has BioMed Central