Joyce Slingerland, MD, PhD, FRCP(C)

Most cells in adult breast tissue are not growing. Only a small population of progenitor or "stem cells" in the normal breast can renew themselves and these can give rise to cancer. The cancer stem cells can survive chemotherapy and radiation therapy and lead to breast cancer recurrence. Since breast cancer stem cells are the most resilient, these cells may the cause of metastasis and patient death from breast cancer. Also, obesity is a risk factor for the development of post-menopausal breast cancer and predicts worse outcome for all breast cancers. Since early in tumor invasion, breast cells must invade into surrounding fat, Dr. Slingerland's team studied how fat cells affect the stem cell population in normal and malignant breast cells. In previous studies, they showed that growth of breast cancer cells with fat cells increases the malignancy of the cancers, which makes the cancer cells more prone to metastasis. After exposure to fat cells, the cancers produce several protein growth factors or cytokines and VEGF and these drive an increase in the cancer stem cell activity to increase cancer growth and dramatically increase metastasis in laboratory models. VEGF was thus shown to have a new role as a cancer stem cell factor. This work may explain the link between increased breast cancer risk and poor outcome associated with obesity. It also suggests that anti-VEGF drugs may work to block cancer stem cells in addition to their known effects on angiogenesis.

Mid-year Progress: There is increasing evidence to suggest that breast cancers arise from malignant stem cell populations. The "cancer stem cells" survive chemo and radiation therapy leading to breast cancer recurrence, which ultimately cause metastasis and patient death. Thus, scientists need to better understand how breast stem cells are regulated by surrounding fat cells and cells at metastatic sites. Dr. Slingerland's past BCRF-funded work showed that fat cells and cancer stem cells interact to increase production of proteins that drive cancer stem cell growth and promote cancer metastasis. This work may explain the link between increased breast cancer risk and poor outcome associated with obesity. Ongoing efforts are underway to develop stem cell targeted therapies.

Bio:
A native of Canada, Dr. Slingerland received her MD from the University of Toronto in 1983, followed by a Fellowship in Internal Medicine with the Royal College of Physicians and Surgeons in Canada. In 1987, she was certified by the American Board in Internal Medicine and in Medical Oncology by the Royal College of Physicians and Surgeons. In August of 2002, Dr. Slingerland came to the University of Miami Miller School of Medicine as the Director of the Braman Breast Cancer Institute, Sylvester Comprehensive Cancer Center (SCCC) where she has worked to expand and coordinate research efforts on breast cancer from many disciplines. In addition, she is co-leader of the Breast Cancer Program at SCCC, and a tenured Professor in the Departments of Medicine and Biochemistry & Molecular Biology.

Dr. Slingerland discovered the cell cycle inhibitor p27 and her research investigates regulation of the G1 to S phase transition and how the cell cycle regulators are disrupted in cancer through aberrant signal transduction. Current work also investigates reversal of antiestrogen resistance in breast cancer through targeted therapies. She has published over 70 articles and reviews in addition to several book chapters and has received numerous awards. Dr. Slingerland continues her medical practice devoted entirely to breast cancer patients at the Sylvester Comprehensive Cancer Center and the Jackson Memorial Hospital.