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Ronald B. Herberman, M.D.

Ronald B. Herberman, M.D.

University Of Pittsburgh Cancer Institute Breast Cancer Researchers Win Grants Funded By State Income Tax Refunds

PITTSBURGH, April 4, 2001 — The Pennsylvania Department of Health's Cancer Control Program has awarded four researchers associated with the University of Pittsburgh Cancer Institute (UPCI) grants to study breast cancer through an initiative funded by taxpayers who donated their state income tax refunds to the Breast and Cervical Cancer Research Fund. The UPCI researchers received four of the eight grants awarded this year, each totaling $35,000.

The announcement of grant recipients was made by Michele M. Ridge, First Lady of the Commonwealth, and Robert S. Zimmerman, Secretary of Health, as well as by Pat Halpin-Murphy, president and founder of the Pennsylvania Breast Cancer Coalition (PBCC), at a press conference held today at UPCI.

Grants to UPCI investigators all focus on the role of estrogen in breast cancer, including biochemical, genetic and tissue studies that should improve the understanding of breast cancer risk and the development of highly specific hormone-based therapies against this disease.

UPCI's grant recipients are Jean J. Latimer, Ph.D., assistant professor of obstetrics/gynecology and reproductive sciences, University of Pittsburgh School of Medicine and Magee-Womens Research Institute; Kenneth McCarty, Jr., M.D., Ph.D., professor of medicine and pathology, University of Pittsburgh School of Medicine; Francesmary Modugno, Ph.D., M.P.H., assistant professor of epidemiology, University of Pittsburgh Graduate School of Public Health; and Mark Nichols, Ph.D., assistant professor of pharmacology, University of Pittsburgh School of Medicine. Dr. Latimer's grant was awarded to Magee-Womens Hospital of University of Pittsburgh Medical Center. The other three were awarded to the University of Pittsburgh. All four recipients are members of UPCI.

Researchers from the University of Pennsylvania, Temple University and Penn State University received the state's four other awards.

"UPCI investigators have received 12 of the 25 grants awarded in the three years this program has been in existence. The grants are very important in that they enable these researchers to conduct preliminary studies and obtain additional findings that become the basis for obtaining major grant support from sources such as the National Institutes of Health. In effect, each dollar donated through the tax check-off initiative is leveraged to far more research dedicated to the understanding of and cure for breast or cervical cancer," said Ronald B. Herberman, M.D., director of UPCI and associate vice chancellor for research, Health Sciences, University of Pittsburgh.

Taxpayers can indicate their desire to donate all or a portion of their refunds to one of five causes, including breast and cervical cancer research, by “checking off” the line on their state income tax form. During the 1999 tax season, $194,788 was raised; more than $700,000 has been raised since the check-off program was initiated in 1997.

The grants are overseen by the Department of Health's Cancer Control Program. Grant applications are reviewed by the Income Tax Check-Off Committee of the Pennsylvania Cancer Control, Prevention and Research Advisory Board, which is chaired by the PBCC's Ms. Halpin-Murphy, who is also a breast cancer survivor. PBCC was instrumental in getting legislation passed to create the check-off program. The grants are intended to serve as seed money for researchers, enabling them to apply for larger grants from major funding sources.

Descriptions of the four UPCI and Magee/UPCI projects are as follows:

Dr. Latimer’s project looks at what effects the anti-breast cancer drugs known as selective estrogen response modifiers (SERMs) have on breast cancer tissue cultures. Studies of SERMs in culture models she has developed should help reveal how these agents act at the tissue level to enable better treatments for cancer or to prevent its development altogether. A prior tax check-off grant awardee, Dr. Latimer has uncovered important information about the genetic repair mechanisms that go awry and lead to breast cancer. In addition, she has developed one of the few cell culture systems that mimic the structure of the human breast for the study of normal breast tissue, breast cancer cells and non-tumor tissue growing next to tumors. Called mammospheres, these clusters of breast cells not only are three-dimensional, but their long-term viability allows for growth and differentiation into complex branching ducts and lobules that look very much like the milk plumbing system of a normal breast. To aid in her research, Dr. Latimer’s laboratory has been using unique time-lapse digital imaging that captures eight hours of living cell movements and cell-to-cell interactions, such as the formation of the epithelial cell architecture.

Drs. McCarty's and Nichols' projects both focus on trying to understand why some women do not respond to SERMs, including tamoxifen. Through their research, they hope to develop more sensitive screenings to identify those women not likely to respond and by discovering unique aspects of the molecular signaling mechanisms to estrogens and anti-estrogens, their work can enable progress to be made to develop more effective treatments and prevention strategies. SERMs are indicated for women who, through certain tests, are found to have estrogen receptors in their breast cancer tumors. In most cases, SERMs are highly effective in treating breast cancer. But such tests fail to correlate with response in more than 30 percent of breast cancer patients. Addressing this problem lies in determining whether estrogen receptors present in breast cancer cells function normally and therefore respond as expected to tamoxifen. Using a unique assay system, these investigators also are studying how the estrogen receptor functions together with specific co-factors in the cell that control the response of the cell to estrogens. Already, they have identified specific defects in co-activator interactions that should lead to a better understanding of anti-estrogen resistance. Understanding the way that the cells become resistant to the treatment will permit the design of improved therapies that will overcome this resistance.

Dr. Modugno's project looks at the role of body mass index (BMI) and estrogen metabolism in breast cancer associated with hormone replacement therapy (HRT). Through this research, Dr. Modugno and her colleagues may be able to help identify women who would be at an increased risk of breast cancer if they used HRT. HRT is commonly prescribed to alleviate menopausal symptoms such as hot flashes. It has also been shown to reduce the risk of osteoporotic fractures and may have some cardiovascular benefits. Unfortunately, evidence suggests that HRT may increase the risk of breast cancer in post-menopausal women. HRT contains estrogen, a hormone believed to play a role in breast cancer development. In particular, the body metabolizes estrogen to a variety of compounds, and how a woman metabolizes estrogen may affect her risk of breast cancer. Estrogen metabolism is determined by individual biologic and genetic factors. BMI may be one such factor. By identifying factors that alter the risk for breast cancer associated with HRT, this research will help women and their physicians make more informed decisions about using HRT.

Western Pennsylvania’s only National Cancer Institute-designated comprehensive cancer center, UPCI serves a population of more than 6 million people and is a leader in translational research, the conversion of laboratory findings into applications of potential clinical importance. Physicians at UPCI use a wide range of modern technologies and facilities to help each patient receive individualized, comprehensive care. Ongoing studies at the institute lay the foundation for future diagnostic methods and treatments that often become employed nationally and internationally.

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