George W. Sledge, MD

2007-2008 BCRF Project:
BCRF-funded studies under Dr. Sledge's direction at Indiana University led to the development of crucial proof-of-concept trials targeting new blood vessel formation (anti-angiogenic therapy). They now propose to build on this success, examining 1) the interaction of subtle genetic changes (called single nucleotide polymorphisms) with new blood vessel formation in breast cancer patients; 2) the role of anti-angiogenic therapy in lymphedema (arm swelling) in breast cancer survivors, and 3) the interaction of endothelial (blood vessel) precursor cells with breast cancer.

In BCRF-sponsored research, Dr. Sledge and his colleagues continue to investigate novel therapies targeting cancer blood vessels, and the means by which cancers develop resistance to these therapies. Of note, BCRF-funded research represented the intellectual basis for the largest single advance in HER-2-negative metastatic breast cancer in the past 30 years: the combination of bevacizumab (Avastin) plus paclitaxel proving superior to paclitaxel alone with regard to its primary endpoint (progression free survival) as well as with regard to its secondary endpoints of response rate and overall survival. The improvement in Progression Free Survival was from six to almost eleven months.

The researchers are currently investigating the role of differences in host (patient) DNA in determining blood vessel production in breast cancer patients (through the BCRF-supported Friends For Life program) and the effect of such host differences on response to bevacizumab (in the E2100 metastatic trial); the analysis has been completed and will be submitted for presentation at the 2007 San Antonio Symposium. With funds from BCRF supporting Dr. Sledge’s work, one of his Indiana University collaborators, Dr. Bryan Schneider, created the Friends for Life volunteers in order to develop a large grassroots, epidemiologic study, to look at differences between women with and without breast cancer in their inherent (host-related) ability to form new blood vessels.

Mid-Year Progress Report:
BCRF-funded studies at Indiana University led to the development of crucial proof-of-concept trials targeting new blood vessel formation (antiangiogenic therapy). Dr. Sledge and colleagues continue to build on this success, examining 1) the interaction of subtle genetic changes (called single nucleotide polymorphisms) with new blood vessel formation in breast cancer patients; 2) the development of resistance to VEGF- and vascular targeting agents; 3) the interaction of endothelial (blood vessel) precursor cells with breast cancer. In total, they seek to understand the role of new blood vessels in breast cancer and means by which they might be used to improve breast cancer therapy.

Bio:
George Sledge is Professor of Medicine and Pathology at the Indiana University School of Medicine, where he is the Ballve-Lantero Professor of Oncology (Endowed Chair). He is the author of more than 100 scientific publications, most of which deal with the biology and treatment of breast cancer. He serves on numerous national committees, including the Food and Drug Administration's Oncology Drug Advisory Committee and the Department of Defense Breast Cancer Research Program's Integration Panel. He is Editor-In-Chief of the journal Clinical Breast Cancer, is currently chairman of the Eastern Cooperative Oncology Group's Breast Cancer Committee, and serves as a board member for the American Society of Clinical Oncology.

Dr. Sledge's work has focused in recent years on novel biologic therapies for breast cancer. He has led a recent Eastern Cooperative Oncology Group trial examining the safety of trastuzumab and paclitaxel as adjuvant therapy for breast cancer, and led the first ever trial of anti-VEGF monoclonal antibody for metastatic breast cancer. His laboratory interests, supported by The Breast Cancer Research Foundation, have investigated novel anti-angiogenic therapies (treatments designed to prevent the development of new blood vessels in human cancers).