A team of City of Hope scientists is developing a new way to identify women at risk for breast cancer with the help of a $250,000 grant from the Susan G. Komen Breast Cancer Foundation.
The four-phase study takes the concept of genetic research into breast cancer risk a step further. Past studies have indicated an increased risk of breast cancer when a mutation is discovered in the breast cancer genes BRCA1 and BRCA2. Screening for patients possessing BRCA1 and 2 mutations, however, identifies only a very small fraction of women at risk.
City of Hope scientists will statistically analyze gene expression patterns from breast tumors in several independent studies to identify new gene targets and risk-associated mutations potentially influencing their expression. Ultimately, when integrated in screening practices, this will allow many more women a better sense of their risk for disease.
Garry Larson, Ph.D., associate research scientist in the Division of Molecular Medicine, said the first phase will involve reviewing several gene expression studies at other institutions to develop a statistically robust "shopping list" of genes. Bioinformatics and prior clinical studies exploring the genetic stability of breast tumors will be employed to prioritize this list of genes.
The second phase will involve genetic analyses in affected sibling pair families with breast cancer (pairs of sisters that both have breast cancer) that share genetic intervals containing these genes more often than expected by chance. In the third phase, the DNA sequences of identical genes from primates and a wide spectrum of mammals will be examined to see how control elements in these genes survived through evolution.
Ultimately, medical resequencing of select breast cancer patients will be performed to identify gene defects in these control elements. Lastly, they will initiate studies to compare the gene expression of normal and mutant control elements in in vitro systems. Through this process, the research team hopes to identify mutations in genes that can be used for screening to give women a better idea of risk, and reduce anxiety for those currently considered at-risk.
Larson said this study could eventually lead to more effective treatment of breast cancer. "If we can combine the gene expression pattern with genetic makeup, we might be able to identify patients who are responders versus nonresponders to clinical treatment," he said.
The team of researchers includes David Smith, Ph.D., associate research scientist in the Division of Information Sciences, Carlotta Glackin, Ph.D., associate professor, Division of Molecular Medicine, and Jeffrey N. Weitzel, M.D., director of the Department of Clinical Cancer Genetics.
For more than 20 years, the Susan G. Komen Breast Cancer Foundation has been a global leader in the fight against breast cancer through its support of innovative research and community-based outreach programs.