Carol J. Fabian, MD

Although large primary prevention trials have confirmed that the incidence of breast cancer can be reduced by certain drugs (tamoxifen, raloxifene), future generations of promising interventions will be initially tested by small trials that use tissue-based assessments to demonstrate potential effectiveness. A well-accepted technique known as random periareolar fine needle aspiration (RPFNA) can be used to acquire benign breast cells that can be assessed for features associated with the risk of developing breast cancer, and modulation of these features or biomarkers after an intervention. Successful trials demonstrating modulation of "response biomarkers" often associated with cell growth have been conducted with premenopausal women and postmenopausal women taking hormones. Although risk for breast cancer increases with age, postmenopausal women not on hormones typically yield few benign epithelial cells by RPFNA; and so it has been difficult to conduct clinical prevention trials targeted at this cohort.

Dr. Fabian and her colleagues will address this problem by employing ultrasensitive techniques to measure low levels of hormones in small amounts of breast tissue acquired by RPFNA. They will assess expression of critical genes using qRT-PCR which allows assessment even on very small numbers of cells. By developing effective biomarkers for assessment of response, they will facilitate the conduct of tissue-based prevention trials for the majority of postmenopausal women and allow the testing of not only novel drugs and natural products, but also lifestyle modifications such as diet and exercise.

Mid-year Progress Report:
This project is focused on developing better methods of measuring low levels of hormones and gene expression in small amounts of breast tissue acquired from post-menopausal women who are not taking hormone replacement therapy (HRT). This will allow better assessment of response to interventions that are designed to prevent the development of breast cancer. In clinical intervention trials, the researchers routinely use a technique called random periareolar fine needle aspiration (RPFNA) to acquire small amounts of breast tissue. For hormone analysis, they are developing a novel mass spectroscopy approach with investigators at Kansas State University. The preliminary development has been accomplished and validation tests are underway. For gene expression, they use the technique of quantitative real time polymerase chain reaction (qRT-PCR). To date, they have continued development of the reagents and techniques for qRT-PCR. The gene markers have performed well in benign breast tissue and in three breast cancer cell lines used for development, as well as in preliminary testing of RPFNA specimens acquired from three peri-menopausal women. The researchers are now poised to begin the planned assessment of hormone levels and gene expression in 75 post-menopausal women not on HRT, 25 post-menopausal women on HRT, and an additional 22 pre-menopausal women.

Bio:
Carol Fabian received her MD, internal medicine and oncology training from the University of Kansas School of Medicine in Kansas City, Kansas. Dr. Fabian joined the faculty at the University of Kansas Medical Center in 1977 and currently holds the rank of Professor. She serves as the Director of the Breast Cancer Prevention and Survivorship Centers. These Centers are heavily involved in translational research in addition to providing clinical services. She leads the Cancer Prevention Research Program within the University of Kansas Cancer Center and holds the Kansas Masonic Cancer Research Chair.

Dr. Fabian pioneered the use of random periareolar fine needle aspiration to acquire breast epithelial cells for refinement of breast cancer risk assessment and for evaluation of biomarkers as a means of monitoring response in early phase breast cancer prevention clinical trials. Subsequently she has trained investigators at multiple institutions in the use of this technique for research purposes. She is currently the PI of three NCI funded grants assessing the effects on breast cancer risk biomarkers of potential prevention strategies: 1) weight loss; 2) a flaxseed derivative; and 3) an aromatase inhibitor in postmenopausal women taking hormone replacement. The translational nature of her work and long-term relationships with her basic science colleagues in cancer biology (Bruce F. Kimler, PhD) and reproductive endocrinology veterinary medicine (Brian K. Petroff, DVM, PhD) have facilitated the development of this BRCF project.