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BCRF Grantee Since

2005

Donor Recognition

The Celebrity Cruises Award

James M. Ford, MD

Associate Professor of Medicine
Pediatrics and Genetics
Director, Stanford Program for Clinical Cancer Genetics
Stanford University School of Medicine
Stanford, California

Current Research

Co-Investigator: Mark Pegram, MD, Stanford University School of Medicine, Stanford, CA

Sporadic triple negative breast cancers (TNBCs) share many pathologic and molecular features with breast cancers due to hereditary BRCA1 gene mutations, including sensitivity to platinum chemotherapy drugs. Several clinical trials have tested cisplatin or carboplatin as pre-operative therapy for surgically resectable TNBCs. Not all patients respond to this regimen, and predictive molecular signatures are needed to better select patients for this approach to therapy. Drs. Ford and Pegram have independently collected patient tumor samples from clinical trials of pre-operative platinum based chemotherapy. They will now collaborate to measure expression of all genes in these samples and attempt to identify profiles that best predict for chemosensitivity. Ultimately, they hope to use such a predictive gene expression signature to prospectively select patients most likely to benefit from platinum based therapies, as well as others that target DNA repair pathways, such as PARP inhibitors.

Mid-Year Summary

Project 1: Improving Breast Cancer Genetic Risk Assessment:

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 we do not know whether these tests will improve patient care. Using more than 400 research blood samples provided by patients referred to the Stanford Cancer Genetics Program for clinical BRCA1/2 gene mutation testing, the researchers performed high-throughput, multi-gene sequencing to identify risk-associated variants in 42 cancer-related genes. Extensive clinical, demographic and epidemiologic data was gathered for all study participants and analyzed together with results of multi-gene panel testing. Their initial results in both a discovery set of 198 samples and a validation set of 240 samples found that approximately 10% of non-BRCA1/2 carriers carry a potentially pathogenic germline variant in another cancer susceptibility gene. Per participant, the average number of variants of uncertain significance (VUS) across all genes was 2.1. The researchers are currently analyzing their risk profiles based on genetic and family information. Patients with newly identified pathogenic variants were invited for confirmatory clinical testing, genetic counseling and screening recommendations. Disclosure of research testing results to participants who donated specimens several years previously appears feasible and well-tolerated. 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.

Project 2: Gene Expression Profiles in Triple-Negative Breast Cancer: Predicting Platinum Sensitivity:

Sporadic triple-negative breast cancers (TNBCs) share many pathologic and molecular features with breast cancers due to hereditary BRCA1 gene mutations, including sensitivity to platinum chemotherapy drugs. Several clinical trials have tested cisplatin or carboplatin as pre-operative therapy for surgically resectable TNBCs. Not all patients respond to this regimen, and predictive molecular signatures are needed to better select patients for this approach to therapy. Drs. Ford and Pegram have independently collected patient tumor samples from clinical trials of pre-operative platinum based chemotherapy. In the first six months of this project the Pegram laboratory has performed extensive gene expression studies on 125 samples from their cohort of platinum treated TNBC patients and analyzed them with regard to clinical response. Specific sets of genes have been identified that predict for response and survival. They will now collaborate with Dr. Ford to measure expression of all genes in their respective sample sets and to identify profiles that best predict for chemosensitivity. Ultimately, they hope to use such a predictive gene expression signature to prospectively select patients most likely to benefit from platinum based therapies, as well as others that target DNA repair pathways, such as PARP inhibitors.

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.

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Co-Investigators