Christine Ambrosone, PhD

2008-2009 BCRF Project:
Compared to Caucasian women, 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. Currently, the reasons for these differences in breast cancer are largely unknown.

Vitamin D, obtained from sunlight and from some foods and supplements, is required for human health, and there is increasing interest in Vitamin D's anti-cancer activities. Vitamin D levels are consistently lower in blacks than in whites, and low Vitamin D levels are associated with risk of aggressive prostate cancer in men, and higher overall cancer mortality among black men.

In an ongoing case-control study of breast cancer in black and white women, Dr. Ambrosone will characterize these aggressive breast cancers using specific markers in breast tumors, and test for relationships between Vitamin D levels, differences in the receptor in Vitamin D, and aggressive breast cancer in black and white women. Adequate Vitamin D can be readily obtained by simply increasing sun exposure and/or use of dietary supplements. Thus, findings from this study could have a direct impact on reducing risk of aggressive breast cancers among black and white women.

Mid-year Progress Report:
Because black women are more likely than white women to be diagnosed with a more aggressive form of breast cancer, Dr. Ambrosone and her team are conducting a study to determine what the causes of these differences may be. They received funding from BCRF to obtain blocks with tumors from hospitals where women who participated in their study had their surgery, to make panels where a number of tissues can be studied at the same time (called tissue microarrays [TMAs]), and to stain for the markers that characterize these more aggressive tumors.

Since receiving funding, the researchers have received 130 blocks, for a total of 488. Approximately two-thirds of these tumors have been evaluated by the pathologist, and are ready to be made into the TMAs. The researchers have done staining on practice TMAs to be sure that the assays are staining properly. They also hypothesize that one reason for more aggressive breast cancers could be due to lower levels of vitamin D in black women, due to darker skin pigmentation, which blocks the sun’s rays.

During the last six months, they conducted pilot work, using samples from another study, and tested laboratories for the most reliable measurement of vitamin D in the blood. In so doing, the scientists found that lower levels were associated with more aggressive breast cancers, supporting their hypothesis. They also sequenced the gene for vitamin D receptor in samples from black and white women and identified specific DNA changes that represent the differences across the gene. These analyses form the basis for the assays to be conducted in the case-control study during the next six months.

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 Senior Editor for Cancer Research, and is on the Board of Scientific Advisors to the Director of the National Cancer Institute.