Through the study of breast cancer outcomes data, we seek to inform treatment practices and improve patient care for breast cancer. We are currently investigating national as well as institutional level data to 1) characterize practice patterns for patients with ductal carcinoma in situ (DCIS) across the U.S.; 2) understand the implications of new consensus guidelines on margin status for early stage breast cancers from the Society of Surgical Oncology and American Society for Radiation Oncology on reexcision lumpectomy rates for breast conserving surgery, 3) explore the role of racial disparities among breast cancer screening and treatment programs.

Faculty

• Krontiras, Helen, M.D.
• Lancaster, Rachael, B., M.D.
• Parker, Catherine C., M.D.

Chemopreventive agents must be administered on a long-term basis to healthy individuals; hence, emphasis must be placed not only on efficacy but also on a high level of safety. In addition, cancers develop through a multistep process in which molecular and biochemical alterations accumulate in target cells over long periods of time, the end result of which is a clinically apparent malignancy. Development of effective chemopreventive agents, or combinations of agents requires identification of the points in this process in which intervention with a pharmacologic agent or changes in diet through consumption of natural botanicals or modification of diet-related components could inhibit, reverse and/or delay development of invasive and/or metastatic cancers and a knowledge of their mechanisms of action.

Neuroendocrine (NE) tumors are the second most common cause of isolated hepatic metastases. These tumors often cause debilitating symptoms due to excessive hormonal secretion which characterize these NE lesions. Besides surgery, there are limited curative and palliative treatments available to patients with NE tumors, emphasizing the need for development of other forms of therapy. Notch1 is a multi-functional transmembrane receptor that plays an important role in cellular differentiation in the gastrointestinal (GI) tract. Similar to its role in developing nervous tissues, Notch1 signaling is thought to mediate a process called lateral inhibition within the GI tract. During GI development, multipotent cells destined to differentiate into enteroendocrine cells express the Notch1 ligand, Delta. Delta then binds to Notch1 receptors on neighboring undifferentiated cells. This triggers activation of Notch1 within the undifferentiated cells, leading to a cascade that inhibits the expression of pro-endocrine genes. Thus, the overall effect is to limit the number of cells which can differentiate into enteroendocrine cells. The lab has recently shown that over expression of Notch1 in GI carcinoid cells as well as in medullary thyroid cancer cells causes a dramatic reduction in hormone production accompanied by growth suppression. His group is currently developing animal models of GI carcinoid and medullary thyroid tumor progression to investigate the possible role of Notch1 in suppressing hormone production by these tumors. This group is also initiating clinical trails with Notch1 activating compounds.