Nadine M. Tung, MD

2007-2008 BCRF Project:
Co-Investigator: Stuart Schnitt, MD, Beth Israel Deaconess Medical Center, Boston

Most of the breast cancers that develop in women who carry a BRCA1 mutation have a distinct appearance under the microscope. The cells that make up these cancers are poorly differentiated and usually do not contain estrogen receptors (ER) or progesterone receptors, and they usually do not show excess expression of the HER2 oncogene (so-called "triple negative" breast cancers). However, at least 20% of the breast cancers that develop in BRCA1 mutation carriers do in fact contain estrogen receptors.

Very little is known about these breast cancers. In particular it is not known if they actually develop as a result of the BRCA1 mutation or whether they develop from the same causes as non-inherited breast cancers. Understanding these ER-expressing breast cancers is important in order to know how to treat them and prevent them. If, like the triple negative breast cancers, they lack a functioning BRCA1 protein, then the same treatments and prevention agents should be effective for both ER positive and negative BRCA1-associated breast cancers. On the other hand, if the ER positive cancers do not originate from the same mutational mechanism, then treatments and prevention agents used for ER positive breast cancers in the general population might be more appropriate.

In this project, Drs. Tung and Schnitt will analyze whether ER positive breast cancers in women with a BRCA1 mutation lack BRCA1 protein expression, like the triple negative breast cancers, or whether they have a functioning BRCA1 protein. They will also look at other protein stains to try to determine if the ER positive and negative breast cancers originate in the same way. This might give researchers clues as to whether to use similar drugs to try to prevent both types of breast cancers. Finally, the investigators will try to determine whether there are any clinical factors that can help predict whether a woman with a BRCA1 mutation is more likely to develop an ER-positive or ER-negative breast cancer.

Mid-Year Progress Report:
Drs. Tung and Schnitt report that IRB approval was granted on October 31, 2007. During the first three months of the project, they have been identifying and collecting tumor blocks and slides of the breast cancers from BRCA1 mutation carriers at the Beth Israel Deaconess Medical Center and Dana Farber Cancer Institute. Since there is no report in the literature describing the pathology of ER+ BRCA1-associated breast cancers, they initially reviewed the first 19 cases collected. An abstract describing these cancers has been accepted for presentation at the US and Canadian Academy of Pathology meeting in Denver, CO in March 2008. To date, the researchers have obtained and analyzed an additional 13 ER+ BRCA1-associated breast cancers and have identified 28 others for review.

As cases are obtained, clinical data is being collected to determine any factors in this population which predict for the development of an ER+ breast cancer. Once the sufficient number of ER+ (60 cases) and ER- breast cancers (at least 60; they expect 200) have been collected, tissue microarrays (TMAs) will be constructed. TMAs are an efficient platform to analyze large numbers of cases. At that time, the specimens will be studied to evaluate differences in the loss of the BRCA1 protein and expression of other biological markers in the ER+ compared to the ER- cancers. The scientists' goal is to construct the TMAs by May so staining of the tissue and data analysis can begin.

Bio:
Nadine Tung, M.D. is the Director of the Cancer Risk Evaluation Program at Beth Israel Deaconess Medical Center in Boston. She is an active member of the Dana Farber/ Harvard Cancer Center, an attending physician in the medical oncology division at Beth Israel Deaconess Medical Center, and as assistant professor of Medicine at Harvard Medical School. Her research focuses on genetic causes of cancer and as well as effective strategies for cancer prevention and early detection.

Dr. Tung earned her undergraduate degree at Princeton University and attended Harvard Medical School. She completed her internship, residence and hematology- oncology fellowship at Beth Israel hospital in Boston before joining the staff in 1990 as an attending physician.