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Mary L. Smith Charitable Lead Trust and Pfeiffer Research Foundation Award Grants for Studies of Estrogen and Breast Cancer by Fox Chase Pharmacogeneticist

PHILADELPHIA (September 9, 1999) -- Dr. Rebecca B. Raftogianis of Elkins Park, Pa., a researcher in Fox Chase Cancer Center's department of pharmacology, has received two grants from area foundations to support her studies of genetic factors governing estrogen metabolism and its possible role in the development of breast cancer.

A one-year grant of $64,000 from the Mary L. Smith Charitable Lead Trust of Newtown Square, Pa., will fund a project on genetic factors that might predict a woman's response to breast-cancer medications. A one-year grant of $74,650 from the Gustavus and Louise Pfeiffer Research Foundation in Denville, N.J., will support a study of genetic factors contributing to the cancer-causing ability of estrogens.

Overall, Raftogianis' research focuses on genetic variations that influence the effect of medicines on different people-an area of study called pharmacogenetics. An important objective is finding individual variations in genes, including those that control how the body makes use of drugs and genes whose products are the targets of certain medications, such as hormone replacement therapy. Ultimately, her goal is to improve the way drugs are used and to develop better drugs by identifying individuals who are likely to benefit from a specific medicine or who are at increased risk of adverse side effects.

Her newest projects address the issue of genetic factors that predispose women to breast cancer. "Specifically, we aim to identify genetic variations in human genes involved in regulating estrogen and determine if they increase the risk of breast cancer," Raftogianis explained.

"Approximately 25 million women in the United States take estrogen-containing drugs each year for birth control and for postmenopausal conditions," she pointed out. "However, lifetime exposure to estrogens has been established as a risk factor for the development of breast cancer. Studies have also suggested that some women have a genetic predisposition for breast cancer that is promoted by estrogen. Avoiding the use of estrogen-containing drugs may be an important cancer prevention measure for these women."

Raftogianis is studying genes that are important as potential breast-cancer risk factors because they help metabolize estrogens in the body. Critical enzyme reactions involving these genes are "sulfation," which makes estrogens inactive, and "desulfation," which makes the sulfated estrogens active again. This system has also been identified as a target for possible new drugs against breast cancer.

"Many breast tumors 'feed' on estrogens and depend on them for growth and progression to invasive breast cancer," said Raftogianis. "If we could identify a drug to decrease the amount of biologically active forms of estrogen that are available to tumor cells, this therapy might slow or stop tumor growth."

Inhibiting the activation of estrogens by the desulfation process is a particularly attractive drug target because the enzyme responsible for this reaction is more active in breast tumor cells than in normal breast cells. One such drug developed at Duquesne University is slated to enter clinical trials soon. Raftogianis is collaborating with researchers there to identify genetic variations that may affect how a woman responds to the drug.

For the Pfeiffer-funded project on genetic factors contributing to the carcinogenicity of estrogens, Raftogianis is working with several Fox Chase researchers, including Dr. Mary B. Daly, director of the Margaret Dyson Family-Risk Assessment Program, and Dr. Andrew K. Godwin, a molecular geneticist who is studying previously unidentified genes that may increase breast-cancer risk.

"As genetic counseling becomes a more frequent and accepted practice, it is imperative that risk factors are clearly defined and widely disseminated," Raftogianis emphasized. "This study should increase knowledge of risk factors and facilitate informed decision-making by clinicians in prescribing estrogen-containing drugs."

Raftogianis received her bachelor of science degree in pharmacy from Albany College of Pharmacy in Albany, N.Y., and her Ph.D. in pharmaceutical chemistry from the University of Utah. She joined Fox Chase in 1998 after postdoctoral training in pharmacogenetics at the Mayo Clinic.

The new grants provide critical start-up funds for Raftogianis' research. In thanking the Mary L. Smith Charitable Lead Trust and the Gustavus and Louise Pfeiffer Research Foundation, Raftogianis and Fox Chase president Dr. Robert C. Young noted that private philanthropic support to young scientists comes at a critical time in their careers.

"Funding from organizations such as yours is crucial not only in getting our work done but also for validating our scientific ideas," said Raftogianis.

"It represents a unique role that private philanthropy can exercise in the development of young scientists and something that I believe deserves special recognition," Young wrote.

The Gustavus and Louise Pfeiffer Research Foundation is a private philanthropic agency that awards grants for the advancement of medicine and pharmacy, including education, health programs and biomedical research.

The Mary L. Smith Charitable Lead Trust awards annual grants to support medical research in the Delaware Valley. Since 1984, the Trust has given Fox Chase Cancer Center 10 competitively awarded grants for cancer research, totaling more than $457,500.

Fox Chase Cancer Center is one of 36 National Cancer Institute-designated comprehensive cancer centers in the nation. The Center's activities include basic and clinical research, prevention, detection and treatment of cancer and community outreach programs.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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