George W. Sledge, Jr., MD
Chief, Division of Oncology
Professor of Medicine
Stanford University School of Medicine
2013-2014 BCRF Project:
(The J.C. Penney Award)
Dr. Sledge continues to study the role of drugs that block new blood vessel growth in breast cancer. A major problem with such drugs is the development of resistance. His work suggests that these drugs cause changes in breast cancers that render them more aggressive. His group has also worked on a new class of drugs (called TORC 1/Torc2 inhibitors) that appear to have significant activity against estrogen-sensitive breast cancer in laboratory models. They are also working on developing agents that might prevent the spread of breast cancers.
In a new BCRF project in 2013-14, Dr. Sledge’s goal is to discover new connections between specific treatments, breast cancer recurrence and survival among more than 15,000 breast cancer patients. While clinical trials are required to test a new drug’s efficacy under controlled conditions, they enroll only 3% of United States cancer patients. Dr. Sledge proposes a complementary strategy to study the real-world effectiveness of breast cancer treatments, in the clinical practice settings where most patients are treated. Until now, knowledge of breast cancer care has been limited by the lack of integrated data on patient demographics, tumor biology, specific therapies and survival, all of which are required to assess an intervention’s benefits and harms. Dr. Sledge and his team surmounted these limitations by developing Oncoshare, a research database of 15,392 breast cancer patients treated from 2000-2011 in academic and community healthcare systems. Oncoshare integrates treatment data from electronic medical records (EMR) with demographic, tumor and survival information from the statewide California Cancer Registry, a component of the nationwide Surveillance, Epidemiology and End Results Program. Along with EMR and registry data, Dr. Sledge's group linked results of genetic tests obtained from testing laboratories, including BRCA1 and BRCA2 and the Oncotype Dx 21-gene recurrence score. These integrated genetic data allow the researchers to evaluate treatments according to a patient’s unique molecular profile. They will leverage Oncoshare, a uniquely comprehensive new breast cancer database, to discover novel information about the effectiveness and toxicity of specific therapies. Their discoveries will guide the rational design of future clinical trials. Specifically, Dr. Sledge and his team will test whether particular chemotherapy drugs, surgical and radiation techniques are more effective in patients with particular inherited genetic characteristics (for example, mutations in BRCA1/2 or other genes on a research multiplex sequencing panel including CHEK2, PALB2, and TP53) or acquired genetic changes in the tumor (for example, a high or intermediate Oncotype Dx recurrence score). They will also test whether specific non-cancer medications (for example, metformin or beta blockers) serve as “unintended therapy,” acting to prevent breast cancer recurrence and death, or, conversely, increasing the side effects of other treatments.
The researchers will use an informatics approach, including linkage of complementary data sources (EMRs, registry, and genetic laboratory reports) and a novel methodology to mine the text of physicians’ clinical notes for data on treatment effectiveness and side effects. The team has previously used this approach to identify drug side effects, demonstrating their ability to discover toxicities two years before their official report by the Food and Drug Administration. They will apply statistical techniques, including logistic regression and recursive partitioning, to identify the patient, tumor and healthcare system factors that predict benefit or harm from specific interventions.
This project offers a unique opportunity to discover the treatment patterns of greatest benefit to specific subgroups of breast cancer patients, which can serve as a guide to design better clinical trials. This novel “big data” approach will inform the development of large national cancer databases, and their application towards advancing breast cancer care.
Dr. George W. Sledge, Jr. was appointed Chief of Oncology in the Department of Medicine at Stanford University Medical Center in January 2013. Prior to joining Stanford, Dr. Sledge was co-Director of the breast cancer program at the Indiana University Cancer Center, where he was a Professor of Medicine and Pathology at the Indiana University Simon Cancer Center. He held the Ballve-Lantero Endowed Chair while at Indiana University.
Dr. Sledge specializes in the study and treatment of breast cancer and directed the first large, nationwide study on the use of paclitaxel to treat advanced breast cancer. His recent research focuses on novel biologic treatments for breast cancer. He has published over 250 articles in medical journals about breast cancer and chaired several nationwide clinical trials involving new breast cancer treatments. His work spans both laboratory and clinic.
Dr. Sledge serves as Editor-in-Chief of the journal Clinical Breast Cancer and is Immediate Past President of the American Society of Clinical Oncology (ASCO). He served as chairman of the Breast Committee of the Eastern Cooperative Oncology Group from 2002-2009, where he played an important role in the development of several nationwide clinical trials. He has also served as chair of ASCO's Education Committee, as a member of the Department of Defense Breast Cancer Research Program's Integration Panel, as a member of the Food and Drug Administration's Oncology Drug Advisory Committee (ODAC), and currently as a member of the External Advisory Committee for The Cancer Genome Atlas (TCGA) project.
Dr. Sledge received the 2006 Komen Foundation Brinker Award for Scientific Distinction in 2006, The Breast Cancer Research Foundation Jill Rose Award and the William L. McGuire Award from the San Antonio Breast Cancer Symposium in 2010.