James M. Ford, MD

2012-2013 BCRF Project:
In a study funded by BCRF, Dr. Ford has completed accrual to a phase II clinical trial of gemcitabine, carboplatin, and iniparib (BSI-201) as pre-operative (neoadjuvant) treatment for women with stage I–III triple negative or BRCA mutation-associated breast cancer. A total of 93 patients were enrolled onto this study, and correlative laboratory studies aim to identify genomics-based signatures that predict clinical outcomes, based on mechanisms for DNA repair.

In 2012-2013, Dr. Ford will undertake a new study on triple negative breast cancer that aims to improve the effectiveness of available tests for genetic risk through the use of new gene sequencing technologies. Currently available tests for the genetic risk of developing breast cancer are uninformative for most patients, even those with family histories strongly suggestive of cancer susceptibility. Emerging technologies allow inexpensive sequencing of multiple genes, but scientists do not yet know whether these tests will improve patient care. Using research blood samples provided by patients referred to the Stanford Cancer Genetics Program for clinical BRCA1/2 gene mutation testing, Dr. Ford’s team will evaluate a high-throughput, multi-gene sequencing technology to identify risk-associated variants in many breast cancer-related genes. Their hypothesis is that the accuracy of breast cancer risk assessment for individual patients can be improved by incorporating emerging genetic tests. They will test this hypothesis by identifying 600 patients with personal or family history suggestive of genetic breast cancer predisposition and test these individuals for mutations or variants in a panel of 62 genes and loci associated with breast cancer risk, hereditary cancer syndromes, and DNA repair.

Mid-year Progress: Thus far, nearly 200 research blood samples have been provided by patients referred to the Stanford Cancer Genetics Program for clinical BRCA1/2 gene mutation testing. Working with these specimens, Dr. Ford's team is using a high-throughput, multi-gene sequencing technology to identify risk-associated variants in many breast cancer-related genes. The researchers' hypothesis is that the accuracy of breast cancer risk assessment for individual patients can be improved by incorporating emerging genetic tests. Dr. Ford's team continues to test this hypothesis by identifying patients with personal or family history suggestive of genetic breast cancer predisposition, and test them for mutations or variants in a panel of 62 genes and loci associated with breast cancer risk, hereditary cancer syndromes, and DNA repair. Genetic testing consists of exome selection techniques on purified genomic DNA, followed by high-throughput, high-coverage sequencing to identify known pathogenic variants and discover novel variants. Extensive clinical, demographic and epidemiologic data is gathered for all study participants and analyzed together with results of multi-gene panel testing. Dr. Ford's team will also will test whether the results of multi-gene panel testing improve upon the ability of various breast cancer risk models' discrimination between women who did, versus who did not, develop breast cancer on ten-year follow-up. Their initial results have identified a number of new deleterious variants unexpected in these patients.

The team is currently analyzing the volunteers' risk profiles based on genetic and family information. Further DNA testing using the gene panel is ongoing. The results of this study have strong potential to guide the translation of emerging genetic tests for clinical use, and to inform the design of a large population-based registry study.

Bio:
Dr. 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.