Gretchen Gierach, Ph.D, M.P.H.
|Organization:||National Cancer InstituteDivision of Cancer Epidemiology & Genetics, Hormonal and Reproductive Epidemiology Branch|
|Address:||NCI Shady GroveRoom 7E108|
Dr. Gierach earned both her M.P.H. (2004) and Ph.D. (2006) degrees in epidemiology from the University of Pittsburgh with a focus in cancer epidemiology and women’s health. Dr. Gierach joined the Hormonal and Reproductive Epidemiology Branch (HREB) as a NCI Cancer Prevention Fellow in 2006 and as an Investigator in 2010. She has been awarded the Division of Cancer Epidemiology and Genetics (DCEG) Molecular Epidemiology Research Funding Award, the NCI Merit Award in Cancer Prevention Research Training, and an Award to Advance Research on Cancers in Women from the NCI Office of Science Planning and Assessment and the NIH Office of Research on Women’s Health. Dr. Gierach serves as DCEG’s representative to the NIH Intramural Program on Research on Women's Health Steering Committee and the NCI Women’s Health Activities Committee, and is an active member of the DENSNP and Marker Of DEnsity (MODE) Consortia on the genetics of mammographic density.
We are interested in the study of the etiology of hormonally-related female cancers, particularly in the molecular mechanisms underlying breast carcinogenesis. We have developed an interdisciplinary research program with a special emphasis on the molecular epidemiology of mammographic density, one of the strongest risk factors for breast cancer.
The tissue composition of the breast is reflected mammographically by the pattern of distribution of fibroglandular and fatty tissue. A higher component of fat results in lower mammographic density. Conversely, a higher proportion of fibroglandular tissue results in greater density. Although high mammographic density is related to some breast cancer risk factors such as nulliparity and menopausal hormone therapy use, studies consistently demonstrate that high mammographic density is an independent risk factor. Therefore, understanding factors that affect mammographic density and their underlying mechanisms are important, yet understudied, research questions.
We successfully competed for funds generated through the sale of U.S. breast cancer postage stamps and in 2007 launched the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project , an interdisciplinary collaboration between HREB investigators and extramural colleagues in the Breast Cancer Surveillance Consortium (BCSC), the University of Vermont, the University of California at San Francisco, and NCI’s Division of Cancer Control and Population Sciences. Recruitment of women ages 40-65 years who have been clinically referred to radiologically-guided breast biopsies was completed in June 2010, with the enrollment of 466 participants. The BREAST Stamp Project aims to characterize the radiologic, histologic, molecular, and biochemical features of dense breast tissue and to understand how the microenvironment of dense breasts promotes neoplastic transformation of the breast epithelium. Risk factor data and biological specimens (blood, buccal cells, tissue fluids, and tissue) required to discover mechanisms and biomarkers that link high mammographic density (as measured quantitatively as an area and volume using computerized methods) to breast cancer risk were collected from study participants.
Although the mechanism by which mammographic density influences breast cancer risk is unknown, the association between elevated mammographic density and breast cancer risk points to an abnormality of the glandular microenvironment. TGF- ß and related factors of shared pathways are promising candidates for markers that may be associated with elevated mammographic density and mediate risk, because they are key regulators of extracellular matrix deposition in the breast. Within the BREAST Stamp Project, we are assessing immunohistochemical expression of proteins in the TGF- ß pathway in breast tissue as they relate to mammographic density. As mammographic density is hypothesized to reflect cumulative exposure to some endogenous growth factors and hormones, we will also relate serum levels of growth factors and hormones to both volumetric and area mammographic density measures within this investigation.
Limited data are available relating mammographic density to molecular markers of breast cancer. To correlate mammographic density to molecular profiles of breast tumors, we are currently leveraging the resources of HREB’s Polish Breast Cancer Study, a population-based case-control study conducted in Lódz and Warsaw from 2000-2003. We have collected mammograms for density assessment from a subset of the Polish Study breast cancer cases with breast tumors that were snap frozen and analyzed using mRNA and cytogenetic profiling. We are examining the relationship between mammographic density, mRNA profiles, and data for protein expression via immunohistochemistry available for over 25 markers previously assessed in the Polish Breast Cancer Study tissue microarrays. If this project reveals possible important relationships between mammogragphic density and tumor profiles, then we will have the opportunity to extend these findings by studying the same relationships in both benign and malignant tumor tissues collected in the BREAST Stamp Project and potentially other studies.
Epidemiologic risk factors strongly associated with mammographic density, such as age and body mass index, explain only about 20% to 30% of the variation in density. The remaining variation in mammographic density is thought to be, in part, genetically-determined. We are therefore conducting several investigations designed to address the role of genes in mammographic density. In collaboration with DCEG’s Clinical Genetics Branch, we are examining whether mammographic density differs by BRCA1/2 mutation status. Within HREB, we are also investing new resources to identify genetic and environmental determinants of breast density among younger women using novel mammography and ultrasound tomography methods to measure breast density as a volume.
In addition to addressing how molecular epidemiologic factors may influence mammographic density and its associated breast cancer risk, we are also addressing other ways in which density may relate to breast carcinogenesis. In collaboration with numerous DCEG and BCSC investigators, we are examining the association between mammographic density and breast cancer survival in the population-based BCSC. An observed association between mammographic density and survival would not only provide additional clues as to the biology underlying the mammographic density-breast cancer relationship, but could also have potential translational relevance.