James M. Ford, MD

2007-2008 BCRF Project:
Drugs which treat high cholesterol, or "statins" such as lovastatin, are approved for use by the FDA, and are safe and well-tolerated. Recent evidence suggests that statins might also prevent breast cancer. Any new cancer prevention method can be tested most quickly, and with fewest patients, in populations at high cancer risk; if promising, it can then be targeted for testing in all patients. One such high-risk group is women with high inherited breast cancer risk, of which there are estimated to be at least 500,000 in the United States. Dr. Ford's laboratory has shown that breast cancer cells missing the BRCA1 breast cancer susceptibility gene are deficient in DNA repair, including that caused by oxidative radicals associated with normal cellular metabolism. Furthermore, they have found in experimental models that lovastatin inhibits this common cause of DNA damage, and does so particularly well in BRCA1 mutant cells. Therefore, statins may be effective and well-tolerated drugs to slow the process of oxidative DNA damage induced breast cancer progression in women carrying BRCA1 mutations, and perhaps in breast cancer more generally.

With funding from BCRF, Dr. Ford's clinical research group is testing whether lovastatin, used for six months by high-risk women, causes a decrease in the proportion of women with abnormal breast duct cells on needle biopsy. His team will also test whether lovastatin can decrease other markers associated with breast cancer risk, including breast appearance on imaging tests, and breast cell growth, genomic changes and DNA repair functions.

Ongoing basic laboratory studies are addressing the molecular mechanism for this observation, using genetic and pharmacologic models to probe the pathway linking the target of statin drugs to cellular proliferation and DNA repair. If lovastatin decreases the rate of abnormal breast cells and other risk-associated markers, it will be a very promising candidate for larger, longer-term studies in women at various levels of breast cancer risk, which could prove that it prevents breast cancer. This clinical trial opened in December 2005, and has begun to enroll patients, with 23 enrolled to date. The researchers expect to reach their accrual goal of 60 women on this clinical trial in 2008.

Mid-Year Progress Report:
Dr. Ford reports that this clinical trial opened in December 2005, and continues to enroll participants actively; it is feasible and well-tolerated. More recently, he and his team proposed a related aim of mapping the geographic and molecular anatomy of abnormal breast tissue in women at high risk of breast cancer, using breast tissue samples collected at the time of preventive mastectomy for cancer risk reduction.

Bio:
Jim Ford is a medical oncologist and geneticist at Stanford, devoted to studying the genetic basis of breast cancer development, treatment and prevention. Dr. Ford graduated in 1984 Magna Cum Laude (Biology) from Yale University where he later received his M.D. degree from the School of Medicine in 1989. He has been intern (1989-90) and resident (1990-91) of internal medicine, Clinical Fellow in Medical Oncology (1991-94), Research Fellow of Biological Sciences (1993-97), Assistant Professor of Medicine (Oncology) and Genetics (1998-2006), Director of the Stanford Oncology Fellowship Training Program, and Director of the Stanford Cancer Genetics Clinic, at the Stanford University Medical Center. Dr. Ford is currently Associate Professor of Medicine, Pediatrics and Genetics, and Director, Stanford Program for Clinical Cancer Genetics.

Dr. Ford's goals are to understand the role of genetic changes in cancer genes in the risk and development of common cancers. He discovered that the p53 and BRCA1 tumor suppressor genes regulate DNA repair, and has developed novel assays to examine DNA repair activity in primary human tissues. He is developing techniques for high-throughput genomic analyses of cancer to identify molecular signatures for targeted therapies.

Dr. Ford's honors and awards include the Etta S. Chidsey Award in Cancer Research from the Yale Comprehensive Cancer Center (1987), NIH K08 Clinical Investigator Award (1995), Second Annual Gerald B. Grindey Memorial Young Investigator Award - AACR (1997), Sidney Kimmel Foundation for Cancer Research Scholar Award (1999), Doris Duke Foundation Clinical Scientist Award in Cancer Etiology and Pathogenesis (1999), Burroughs-Wellcome Fund New Investigator Award in Toxicology (2000), and the V Foundation Translational Research Award. Dr. Ford is an Editor for the journals Cancer Research and DNA Repair, is on the Scientific Review Committee for the V Foundation for Cancer Research, and a Council Member of the California Breast Cancer Research Program.