Information for the Lay Person

In the United States, one in eight women will develop breast cancer during her lifetime. Early detection of breast cancer allows a physician to treat the initial stage of the disease while the tumor is still confined to the breast, increasing the patient’s chance for long-term survival. Once breast cancer spreads, or metastasizes, from the breast to other tissues of the body, therapies are limited, and there is no cure for the disease. While early detection is essential for initiating treatment before metastasis, currently used diagnostic methods for breast cancer have low sensitivity and are far from optimal. Moreover, acquiring tissue through an invasive biopsy or surgery is necessary for the currently available diagnostic markers, bearing a heavy burden on patients. The goal of Dr. Kristi Egland’s research program is to develop a minimally invasive blood test for breast cancer detection that is highly sensitive, allowing for early diagnosis.

It is well established that breast cancer patients often produce antibodies to cancer cells. Cancer cells can have proteins that are present in much higher levels than in normal cells, and the immune system can sense these abnormal tumor proteins. Because it is equipped with an amplification system, the immune system can produce large amounts of antibodies to the abnormal proteins, even when the change in tumor proteins is too small to be detected by current diagnostic tests. Therefore, by detecting the presence of antibodies to a particular tumor antigen, rather than tumor antigen itself, we can achieve high sensitivity allowing earlier diagnosis.

Recently, we isolated a collection of genes, called a library, encoding membrane and secreted proteins from breast cancer cells. Subsequently, the genes in this library that were ubiquitously expressed in normal essential tissues were removed. In order to determine what genes are represented in this library, we obtained DNA sequences of 25,277 of the genes. Secreted and membrane proteins are more likely to induce an antibody response than intracellular proteins. Therefore, this library of clones encoding membrane and secreted tumor antigens is enriched with genes encoding proteins that should preferentially induce an antibody response in patients. We propose that our library encodes numerous tumor antigens and this anti-tumor antibody profile can be used to accurately detect the presence of breast cancer on an individual basis. We are going to use the encoded 100 most abundant library genes to choose the most promising tumor antigen candidates for autoantibody screening. We have established a robust method to produce native antigens that are recognizable by human antibodies. This method is suitable for secreted and membrane proteins and allows the antigens to form higher-order structures necessary for the efficient detection by the antibodies. These native antigens will be generated and screened with patients’ serum as the diagnostic assay.

Detection of a panel of tumor antigens can provide early, specific and personalized diagnosis for breast cancer patients, which will significantly improve outcomes and long-term survival of patients. Early diagnosis is essential in the fight against breast cancer and increases the likelihood of a woman being cured.