James M. Ford, MD, FASCO

Improving breast cancer genetic risk assessment and screening.

Impact

Genetic tests for breast cancer risk can be immensely helpful for families carrying mutations in known breast cancer susceptibility genes, like the BRCA1 and BCRCA2 genes. However, for patients whose inherited risks are not explained by well-known gene mutations, currently available tests provide limited information, do not allow for nuanced genetic counseling on exact levels of risk, and may result in an over-application of prophylactic interventions—such as preventative mastectomies. Researchers have identified approximately 300 potential genetic alterations (known as single nucleotide polymorphisms, SNPs) associated with breast cancer. These are present at varying frequencies in the population and could be used to further refine the percent lifetime risk. Dr. Ford and his team will analyze these SNPs, and how well they coordinate with known risk genes, to potentially improve risk assessments. They are also working to develop new early detection blood-based tools for breast cancer.

Progress Thus Far

Dr. Ford and his team are renowned for establishing that 10-15 percent of women with a personal or family history of breast cancer have mutations in genes other than BRCA1 or BRCA2, including ATM, CDH1, p53, PALB2, CHEK2, and Lynch syndrome genes, expanding the pool of genes that can be integrated into risk assessments. Over two decades of BCRF funding, the team assembled a large biobank, containing thousands of samples from patients with and without a family history of breast cancer. He and his team are expanding the ability to accurately predict genetic breast cancer risk by incorporating Polygenic Risk Scores (PRS) into the analysis of multigene cancer panels. A PRS is an individualized risk assessment calculated by looking at over 300 SNPs. Dr. Ford and his team are applying PRS to samples from carriers of breast cancer susceptibility genes from their biobank, as well as collecting prospective samples from new patients undergoing genetic testing. Using new diagnostic techniques developed at Stanford, they are analyzing cell-free DNA— “liquid biopsies”— as a cancer screening tool to detect cancers at an early and curable stage.

What’s next

Dr. Ford’s team will continue their research to develop accurate PRS in gene mutation carriers and to study novel liquid biopsy technologies for early cancer screening in genetically high-risk populations. The team will analyze blood samples for biomarkers specific to mutant BRCA1and BRCA2 and potential indicators for the early detection of breast cancer in women who are at high risk.