James M. Ford, MD

2008-2009 BCRF Project:
Approximately 15% of all breast cancers, as well as the majority of BRCA1 associated breast cancers, are 'triple negative', lacking expression of estrogen and progesterone receptors, and lacking over-expression or amplification of the HER2/neu oncogene. This is a very aggressive type of breast cancer that disproportionately affects young women and African-Americans, and the best way to treat women with these high-risk breast cancers is still unknown.

Dr. Ford's laboratory has recently shown that triple-negative breast cancer is especially sensitive to specific drugs that target defects in the DNA repair capacity of these cancer cells, including the chemotherapy agents cisplatin and gemcitabine, and a novel class of biologic agents that inhibit the poly-ADP ribose polymerase (PARP) enzyme. The hypothesis of this study is that a combination treatment regimen of gemcitabine, carboplatin, and the PARP inhibitor BSI-201 (produced by a research collaborator, BiPAR Sciences) will yield significant improvement in tumor response among women with early-stage triple negative breast cancer; notably, improved breast tumor response has been proven to predict better survival.

Dr. Ford's team proposes to conduct a Phase II clinical trial of four cycles of gemcitabine, carboplatin and BSI-201, administered every three weeks, in women with Stage II and III triple-negative breast cancer who are eligible to undergo pre-surgical (neoadjuvant) systemic chemotherapy. They will evaluate improvement in breast tumor shrinkage with this regimen compared to other standard regimens, and the secondary translational objectives are to assess the correlation of tumor DNA repair activity and expression of DNA repair genes with tumor response, using novel assays developed in the Ford laboratory on breast tumor specimens which will be collected before and after the investigational treatment. This project has great potential to identify an effective targeted therapy for the 30,000 women who develop triple-negative breast cancer each year in the United States, and to clarify the role of DNA repair pathways in triple-negative breast cancer, which may guide future prevention and treatment approaches.

Mid-year Progress Report:
Dr. Ford and colleagues have now opened a Phase II clinical trial of four cycles of gemcitabine, carboplatin and BSI-201, administered every three weeks, for women with Stage I, II and III triple-negative breast cancer who are eligible to undergo pre-surgical (neoadjuvant) systemic chemotherapy. Their primary objective is to evaluate improvement in breast tumor shrinkage with this regimen, and their secondary translational objectives are to assess the correlation of tumor DNA repair activity and expression of DNA repair genes with tumor response. They have made significant progress in designing and optimizing a correlative laboratory test that determines the DNA repair activity in breast tumor cells collected from women before and after the investigational treatment. They have now shown in the laboratory that this test accurately predicts sensitivity to PARP inhibition in triple-negative breast cancer cells.

Furthermore, they have performed preclinical experiments in triple-negative cell lines that demonstrate synergism between the three drugs being used in this clinical trial; that is, their anti-tumor effects when used together are more than simply additive. This project has great potential to identify an effective targeted therapy for the 30,000 women who develop triple-negative breast cancer each year in the United States, and to clarify the role of DNA repair pathways in this disease, which may guide future prevention and treatment approaches.

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.