Titles and Affiliations
Professor, Department of Oncology
Co-Leader Breast Cancer Program
Lombardi Comprehensive Cancer Center
Research area
Understanding the relationship between obesity, inflammation, and breast cancer risk after menopause.
Impact
Obesity increases the risk of breast cancer after menopause and is associated with a worse outcome in breast cancers diagnosed at any age. Dr. Slingerland is studying how obesity and post-menopausal estrogens increase breast cancer risk and promote estrogen receptor (ER)-positive breast cancer progression to a more aggressive disease. Her work may reveal new strategies for preventing the disease from developing and spreading beyond the breast.
Progress Thus Far
Dr. Slingerland and her team have found that signaling through the estrogen receptor appears to cooperate with obesity-induced inflammation signaling, particularly after menopause. She and her team found that estrone, the main estrogen produced after menopause which is up to two times higher in obese women compared to lean counterparts, contributes to inflammation in the breast and drives metastatic progression. They showed that as breast cancers invade breast fat, contact between breast cancer and the high estrone environment of fat cells stimulates both cell types to secrete cytokines (protein messengers) that increase inflammation, aggressive cancer stem cells, and cancer growth. The team found that two important types of immune cells that normally recognize cancers as foreign and kill them, are inactivated by the inflammation in the breast fat and tumor. In contrast to the major pre-menopausal estrogen that opposes inflammation, estrone, the form of estrogen that dominates after menopause, promotes obesity driven breast inflammation and breast cancer development. They identified an estrone gene signature, a pattern of genes that increase inflammation to turn off immune signaling. This gene profile is not only present in cancer cells but gets activated in normal fat tissues, before cancers arise. Thus, fat cells in the breast become aggressive with obesity and turn off protective immune mechanisms that help a person’s body prevent and fight their cancer.
What’s next
In the next year, Dr. Slingerland and her colleagues will test if new weight loss drugs and exercise can reduce the aggressive form of estrogen in fat, reverse inflammation and wake up immune cells to fight breast cancer. If preclinical studies are successful, they hope to advance these results into new clinical trials to test if weight loss and exercise can counteract “bad” estrogens, block estrone driven metastasis, and improve outcomes.
Biography
Joyce Slingerland, MD, PhD is currently Professor in the department of Oncology and co-Leader of the Breast Cancer Program at Lombardi Comprehensive Cancer Center, Georgetown University. Prior to moving to Georgetown, she was a professor in the Department of Biochemistry and Molecular Biology at the University of Miami, as well as a member of the senior leadership of the University of Miami Sylvester Comprehensive Cancer Center (UMSCCC) and Co-Program Leader of the UMSCCC’s Molecular Oncology and Experimental Therapeutics Program. She has published over 70 articles and reviews in addition to several book chapters and has received numerous awards.
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 School of Medicine as the Director of the Braman Breast Cancer Institute, Sylvester Comprehensive Cancer Center, where she is working to expand and coordinate research efforts on breast cancer from many disciplines.
Dr. Slingerland discovered the “cell growth brakes” molecule p27 and her research investigates how cancer cells lose growth restraints. Current work also investigates the causes underlying resistance to endocrine (also called anti-estrogen) therapies for breast cancer. She is also focused on why obesity increases breast cancer risk and worsens patient outcomes and is testing effects of a fatty environment on breast cancer stem cells.
