Christine B. Ambrosone, PhD

2009-2010 BCRF Project:
In an analysis of vitamin D levels in relation to breast cancer aggressive characteristics last year, Dr. Ambrosone found vitamin D levels were significantly lower in patients with more aggressive cancers, particularly triple-negative breast cancer, which is difficult to treat and more commonly diagnosed in young African-American women. A manuscript of the above results has been submitted for publication. She and her colleagues are now examining vitamin D levels and receptor gene polymorphisms in relation to aggressive breast cancer risk in both African-American and Caucasian women in the Women's Circle of Health Study. Serum samples have been sent to the laboratory for vitamin D measurement and DNA samples have been plated for genotyping. Data analysis and interpretation will be performed within the next 4 months.

Compared to women of European descent, African-American women are more likely to be diagnosed with breast cancer at an earlier age (before age 40), and to have more aggressive breast cancers that are difficult to treat. Scientists do not know the reasons for these differences in breast cancer, making prevention impossible. Many human traits or characteristics evolve over generations in populations and become common.

For example, in Africa, where infectious disease is extremely common, those who have immune systems that can fight off these diseases are more likely to live and go on to have children, with their children having similar immune systems. While a very active immune system may help in fighting off infectious diseases, it also creates an environment in the body that could be related to aggressive cancers. Dr. Ambrosone’s team will compare a number of markers related to the immune system and inflammation between European-American women and African-American women, and test to see if differences in genes that determine these factors are related to breast cancer, especially more aggressive breast cancers at an early age among African-American women.

Mid-Year Progress Report:
Since receipt of BCRF funding in 2009, Dr. Ambrosone's team has measured serum levels of C-reactive protein (CRP) and serum amyloid A (SAA), the two most common markers for inflammatory response. Their results showed that African American (AA) women have higher levels of CRP and SAA than European American (EA) women, and the differences were statistically significant, supporting their hypothesis. These differences appear to be due, in part, to higher body mass index in AA women, which may have an ancestral component.

The researchers are in the process of expanding their blood markers to a panel of 30 immune factors and will compare levels between AA and EA women. They have also extracted DNA from 1,042 AA and 1,307 EA breast cancer cases and controls. They have selected a total number of 157 DNA markers that are related to immune functions. In the next 6 months, they will identify these selected markers on DNA samples they have extracted, and will investigate their contributions to racial differences in breast cancer risk and aggressiveness between AA and EA women.

Bio:
After positions at the National Center for Toxicological Research in Arkansas and Mount Sinai School of Medicine in New York City, Dr. Christine Ambrosone joined the faculty of Roswell Park Cancer Institute (RPCI) in 2002, where she now serves as Chair of the Department of Cancer Prevention and Control.

Dr. Ambrosone is an internationally recognized leader in molecular epidemiology, and is co-founder and past Chairperson of the Molecular Epidemiology Group of the American Association for Cancer Research. She is also active in the Southwest Oncology Group, where she is co-Chair of the Molecular Epidemiology Committee. Her research focuses primarily on breast cancer, and elucidating relationships between exposures, genetic susceptibility and cancer risk and outcomes. One of her main areas of interest in breast cancer is to understand why African-American women are more likely to be diagnosed at a younger age with breast cancer, and to have more aggressive disease characteristics.

Her research also focuses on breast cancer prognosis. Working with SWOG clinicians, Dr. Ambrosone has several ongoing studies targeted at understanding why women with similar disease characteristics and general health status experience different outcomes from chemotherapy, examining the role of inherited differences in metabolism of chemotherapy drugs, as well as modifiable factors, such as vitamin supplements, diet and physical activity. Dr. Ambrosone is Past Senior Editor for Cancer Research, and is on the Board of Scientific Advisors to the Director of the National Cancer Institute.