Approximately two out of every three adults in the U.S. are considered overweight or obese based on Body Mass Index (BMI), a measure calculated from height and weight. Over the past 30 years, U.S. obesity rates have doubled for adults and tripled for children. This trend is also reflected globally, affecting both developed and developing countries, and is attributed to reduced physical activity combined with a diet high in sugar and saturated fat.
The alarming consequence of a greater BMI is a greater risk for many serious health issues, including heart disease, stroke, diabetes, and cancer. The American Institute for Cancer Research estimates that 100,000 of all new cancer cases in the U.S. each year, including breast cancer, are attributable to obesity.
A particularly high obesity-related risk, both in terms of developing and dying from breast cancer, exists for post-menopausal women. After menopause, the risk of obese women developing breast cancer increases by 50% compared to that for those of a healthy weight. Furthermore, it is estimated that an additional 11,000-18,000 deaths per year from recurrent and metastatic breast cancer in U.S. women could be avoided by maintaining a healthy weight throughout adulthood. These statistics combined with the increasing rate of obesity pose a compelling need to understand why and how obesity increases tumor growth and reduces the overall survival of those with breast cancer.
Ofer Reizes, Ph.D., Department of Cell Biology, Lerner Research Institute, is working on answers to these questions. Dr. Reizes' focus has been on the neurobiology of feeding and body weight regulation – research that led him to study the relationship between obesity and breast cancer promotion. Dr. Reizes proposed that excess leptin, a hormone that is secreted from fat and is therefore increased in obese people, stimulates the growth of mammary tumors in overweight and obese individuals by targeting the breast cancer stem cell. (Cancer stem cells are proposed to be a small but significant population of chemo- and radio- therapy-resistant cells within a tumor considered to underlie tumor recurrence and metastasis and contribute to poor prognosis.) Indeed, his team has shown that too much leptin leads to accelerated growth and larger tumors in mice. Furthermore, these tumors exhibit a pathological and molecular signature that is similar to a subset of aggressive human tumors also known as basal-like mammary tumors. In contrast, mutant obese mice that lack leptin exhibit suppressed tumor growth. Dr. Reizes' laboratory further determined that the tumors in these obese, leptin-deficient mice lacked cancer stem cells. Importantly, the data indicate that leptin promotes the survival of the cancer stem cell population in mammary tumors, thus linking this fat-secreted hormone to tumor initiation and recurrence.
Future studies will determine whether leptin serves a similar role in human mammary tumors. This work is unique because it has discovered a testable link, i.e. leptin, between obesity and the promotion of aggressive breast tumors. Building on this discovery may help identify a targeted therapeutic approach to suppress breast tumor growth and thereby offer hope to people threatened by this disease.
Dr. Reizes has been invited to present his findings at several venues, including the June 19-22, 2010, Endocrine Society Annual Meeting in San Diego, CA.