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Discovering the causes of cancer and the means of prevention

Gretchen Gierach Explores the Origins of Breast Cancer

November 2011 - Linkage Newsletter

by Amber K. Boehm, Ph.D.

Hormonally related cancers in women have been a long-term interest for Gretchen L. Gierach, Ph.D., who was appointed as a tenure-track investigator in the Hormonal and Reproductive Epidemiology Branch (HREB) in January 2010. Her interest in women's health began while she was an undergraduate student at Pennsylvania State University. After working for several years in the field of women's health research, she attended the University of Pittsburgh Graduate School of Public Health, Gretchen Gierachwhere she received her M.P.H. and Ph.D. in epidemiology, with an emphasis in women's health and cancer epidemiology.

One of Dr. Gierach's graduate studies focused on mammographic density—that is, the tissue composition of the breast as reflected in a mammogram. High mammographic density is one of the strongest risk factors for breast cancer, and yet little is known about why. Dr. Gierach's work in mammographic density piqued her interest in defining density as an intermediate marker for studying breast cancer etiology.

When Dr. Gierach joined NCI in 2006 as a Cancer Prevention Fellow, HREB Branch Chief Louise A. Brinton, Ph.D., offered her the opportunity to develop and oversee a new project known as the Breast Radiology Evaluation and Study of Tissues (BREAST), which is funded by proceeds from the sale of the U.S. Postal Service Breast Cancer Research Stamp. The study, which Dr. Gierach co-leads with Mark E. Sherman, M.D., a senior clinician in HREB, considers both the radiologic features of the breast through mammography and the histologic, molecular, and biochemical characteristics of breast tissue among women undergoing image-guided breast biopsies at the University of Vermont Breast Cancer Surveillance System site. Dr. Gierach is relating indices of mammographic density to tissue-level biomarkers that may uncover the mechanisms linking high mammographic density to breast cancer risk.

Dr. Gierach and colleagues are currently analyzing data from the BREAST Stamp Project with a focus on relating measures of density to serum levels of growth factors and estrogenic hormones. An exciting and novel aspect of this work is the development of new methods to measure density in specific regions of the breast, as opposed to the more traditional approach that uses a single measure for the entire breast. "This assessment allows us to study the morphologic heterogeneity of breast tissue in the context of epidemiologic risk factors," Dr. Gierach explained. The ability to characterize breast density as a volume as opposed to a two-dimensional area may provide a more thorough and accurate representation of breast tissue composition.

In collaboration with the DCEG Clinical Genetics Branch, Dr. Gierach has reported that mammographic density is similar between cancer-free women with BRCA1/2 mutations, which increase the risk of breast cancer, and women at low-to-average risk of developing breast cancer. This finding raises important questions about the use of mammographic density for risk prediction in women with BRCA1/2 mutations.

Dr. Gierach is launching a new study with Dr. Sherman in Detroit, Michigan, that will use a new technology called ultrasound tomography to characterize changes in breast density, which are thought to correlate with changes in breast cancer risk. Ultrasound tomography measures the density of the entire volume of the breast and does not involve ionizing radiation, thereby permitting researchers to safely take repeated measurements. Dr. Gierach will use ultrasound tomography to define a time course of changes in breast density among women taking tamoxifen, which is known to reduce both breast density and breast cancer risk. This information will enable scientists to explore using breast density as a kind of "biosensor" of tamoxifen response and find out whether ultrasound tomography can be a useful tool in making this determination.

"If we demonstrate the utility of ultrasound tomography as a tool for measuring breast density changes in these participants," Dr. Gierach said, "this study could be a launching point to investigate how specific changes in breast density relate to breast carcinogenesis." Dr. Gierach also noted that the study population will be approximately 50 percent African American, a group that has been underrepresented in studies of breast density to date.

Dr. Gierach is obviously busy with her work at NCI, but she loves every minute of it. "Being able to collaborate with clinicians specializing in breast pathology has greatly enhanced my efforts," she said. "I feel very fortunate to have DCEG colleagues whose research I have admired for so long."