Gene Discovery

William Cance, Department of Surgery; H. Shelton Earp, Departments of Medicine and Pharmacology; Edison Liu, Department of Medicine.

This program applies molecular-biology techniques to identify new genes behind the development of breast cancer. The researchers already have discovered two genes that may be new targets for treatment or molecular markers for diagnosis. The first gene, “focal adhesion kinase,” is present at high levels in breast cancers which have the potential to spread quickly. Screening for the presence of focal adhesion kinase may identify forms of breast cancer that require early, aggressive treatment. In addition, inactivating the gene seems to kill the cells, preventing the formation or the spread of a tumor. Another potential treatment involves the recently discovered gene, “rak,” which causes cells to stop growing; the researchers are investigating the possibility of using rak to prevent the proliferation of cancer cells.

 Molecular Epidemiology

Kathy Conway, Barbara Hulka, Robert Millikan, Beth Newman, Department of Epidemiology; Edison Liu, Department of Medicine.

This program encompasses several epidemiological and molecular studies designed to understand how genes and the environment interact in the development of breast cancer.

One epidemiological study to look for mutations associated with breast cancer, led by Hulka and Liu, uses biopsies from 472 women, 236 of whom developed cancer and 236 of whom did not. The women were selected from a larger pool followed for up to 20 years at the Mayo Clinic in Rochester, Minnesota. By comparing cancerous to benign tissue, the researchers have begun to identify genetic mutations in samples which appear completely normal under the microscope. This work may lead to tests that will help to determine a woman’s risk for developing breast cancer long before any symptoms of disease surface.

Newman heads another epidemiological study designed to determine whether environmental factors (such as smoking, exposure to pesticides, and use of hormone pills) and endogenous influences (such as age at first menstrual cycle and at first pregnancy) correlate with breast cancer characterized by specific genetic mutations. The group collaborates with several cancer investigators, including Conway, who is trying to understand the role of the rare versions of the HRAS gene associated with several kinds of cancer, and including Millikan, who is investigating the causes of a very early form of breast cancer, carcinoma in situ.

In particular, the researchers are investigating potential differences in breast cancer between African American and white women. “African-American women die of breast cancer more often than white women,” says Newman. “It may be because they’re diagnosed later, but they may have a more aggressive form of disease.”

Breast Cancer Screening and Public Health Intervention

Jo Anne Earp and Eugenia Eng, Department of Health Behavior and Health Education; Russell Harris, Department of Medicine; Patricia Braeuning and Etta Pisano, Department of Radiology.

The public health intervention and imaging development projects seek to make mammography more accessible, more widely used, and even more effective.

Braeuning, Pisano, and their colleagues are conducting clinical studies of the use of magnetic resonance imaging and digital mammography in screening women who have had cancer already. The advanced imaging techniques may be more sensitive to small tumors and may provide better contrast between normal or benign tissue and cancerous lesions. The researchers believe that the new imaging techniques will improve the monitoring of high-risk women, possibly providing an alternative to radical surgery.

While development of new imaging systems for mammography proceeds, the North Carolina Breast Cancer Screening Program, headed by Earp, is reaching more African American women with the screening tools currently available. Fewer African American women over 50 receive mammograms, and their mortality rate due to breast cancer is 20 percent higher than that for white women, while the incidences of breast cancer are approximately the same. To help even the odds, Earp, Eng, Harris, and their colleagues are working with health-care professionals and community advisors in five counties in eastern North Carolina to overcome the fears, myths, administrative obstacles, and logistical impediments preventing widespread and regular mammography among African American women.