Andrew Dannenberg, MD
Director of Cancer Prevention at New York Presbyterian Hospital-Cornell
Henry R. Erle, MD-Roberts Family Professor of Medicine
Weill Cornell Medical College
New York, New York
2013-2014 BCRF Project:
(The Bloomingdale's Award)
Obesity is a risk factor for the development of hormone receptor-positive (HR+) post-menopausal breast cancer and possibly triple negative breast cancer. Moreover, obesity is associated with poor outcomes for patients with breast cancer. Dr. Dannenberg’s team was the first to show that obesity causes an inflammatory state with related molecular changes in the human breast. This very recent finding builds upon preclinical studies. The researchers’ ongoing work is focused on determining the mechanisms (cellular, molecular) by which obesity-related breast inflammation occurs and defining the inflammation-related mechanisms that drive tumor formation and progression. They are also identifying biomarkers in blood and urine that reflect obesity-related adipose tissue inflammation, as well as utilizing established preclinical models to develop strategies to reverse obesity-related inflammation with the ultimate goal of reducing the risk of breast cancer. Positive preclinical findings provide the basis for human studies which have already been initiated.
A variety of inflammatory mediators including the products of cyclooxygenase (COX) enzymes stimulate the formation of aromatase, the enzyme that makes estrogen (this female hormone can drive breast cancer formation and growth). During the next year, Dr. Dannenberg will carry out mechanistic studies to explain the link between obesity and breast inflammation with an emphasis on aromatase. Additionally, his team will attempt to develop strategies to reverse obesity-related inflammation with the ultimate goal of reducing the risk of breast cancer.
Obesity is a risk factor for the development of hormone receptor-positive postmenopausal breast cancer.Moreover, obesity has been associated with poor outcomes for breast cancer patients. Chronic inflammation is widely recognized to increase the risk of developing numerous other malignancies. Our laboratory was the first to demonstrate that obesity caused breast inflammation. This inflammatory state is associated with molecular changes that have been linked to the development and progression of breast cancer. In ongoing studies, we are attempting to identify additional factors that have the potential to induce or reverse breast inflammation. In addition to attempting to elucidate the mechanism(s) by which breast inflammation impacts the development and progression of cancer, complementary studies have been initiated to determine the role of blood-derived factors in the pathogenesis of obesity-related breast cancer. Preclinical models continue to be used to identify potential strategies (e.g., caloric restriction, dietary supplement, nonsteroidal anti-inflammatory drugs) to reverse obesity-related adipose inflammation with the ultimate goal of reducing the risk of breast cancer. Based on promising results in model systems, a human study involving a nonsteroidal anti-inflammatory drug is underway. Ultimately, combining both behavioral and pharmacological interventions may prove most practical for attenuating breast inflammation and thereby reducing cancer risk.
Andrew J. Dannenberg, MD is the Henry R. Erle, MD-Roberts Family Professor of Medicine at Weill Cornell Medical College. He is also Director of Cancer Prevention at New York Presbyterian Hospital-Cornell. Dr. Dannenberg received his medical degree from Washington University in St. Louis and served as a medical resident and fellow at The New York Hospital-Cornell Medical Center. He has authored more than 150 scientific articles, as well as edited several books and journals. In 2011, Dr. Dannenberg was awarded the American Association for Cancer Research-Prevent Cancer Foundation award for excellence in cancer prevention research. He is a member of the Association of American Physicians (AAP), the American Society for Clinical Investigation (ASCI), and the American Association for Cancer Research.