Sturgeon given grant to develop blood test for breast cancer

Susan R. Sturgeon, associate professor in the Department of Public Health, has been awarded a two-year, $232,588 by the Susan G. Komen Breast Cancer Foundation to develop a diagnostic blood test for breast cancer.

Sturgeon is working with Kathleen Arcaro, associate professor of Veterinary and Animal Sciences, and Andrea Foulkes, associate professor of Public Health, on the study.

The concept is based on the premise that breast cancer tumors have certain DNA changes known as promoter hypermethylation, and that breast cancer tumors shed sufficient quantities of DNA into the blood to allow detection of the presence of such epigenetic changes. Epigenetic literally means “on the gene,” and promoter hypermethylation is when a methyl molecule is added to the DNA backbone of a gene causing a loss of normal function.

A series of small clinical studies have shown the feasibility of this approach, with moderately high accuracy of breast cancer detection achieved using a relatively small number of genes (usually three to four) in blood. It is likely that expansion of the panel to include other breast-cancer related genes would markedly increase the accuracy of the test. Thus, DNA in serum will be evaluated for promoter hypermethylation in 12 candidate genes from approximately 250 node-positive postmenopausal breast cancer cases, 75 node-negative postmenopausal breast cancer cases, and a comparison group of 250 postmenopausal benign breast disease control subjects who were part of the Mayo Serum Bank, a resource established in the 1970s to identify early markers of breast cancer. The objective will be to determine whether this panel of genes can be used to accurately detect breast cancer.

While early detection by screening mammography has led to a decline in breast cancer mortality over the past decade, mammography has several well-known limitations, including a high rate of false positives, reduced sensitivity in dense breasts, and concerns over radiation exposure, particularly in high-risk women who may benefit by more than annual screening. Limitations of mammography screening combined with a rapid revolution in available molecular tools have led to renewed and vigorous research interest in developing a complementary molecular biomarker for early detection of breast cancer.

Changes in DNA methylation patterns are a common feature of malignant cells, and promoter hypermethylation in key genes is considered one of the most promising biomarkers for a reliable and sensitive screen for early breast cancer.

“Detection of methylation status in serum could lead to the development of an inexpensive, minimally invasive blood test to complement mammography screening<” said Sturgeon. “A methylation-based blood test would be valuable as it could be used between annual mammograms in high-risk women or to evaluate suspicious mammogram findings.”

The test could also assist in identifying women at high-risk of developing breast cancer who may benefit from additional screening methods or other prevention strategies, and could be a valuable intermediate endpoint in chemoprevention trials, she said.

May 21, 2009.