Researcher: Rachel Brem, MD, Associate Professor, Department of Radiology, Director Breast Imaging and Intervention, George Washington University Medical Center, Washington, DC. Project: Efficacy of Ductal Lavage for the Diagnosis of Breast Cancer Award Amount: $10,000 Mammography is currently the most sensitive method of diagnosing breast cancer, but it has a limited specificity. Methods to improve the specificity of breast cancer diagnosis are clearly needed. Dr. Brem intends to assess the sensitivity and specificity of ductal lavage for the diagnosis of breast cancer in women with suspicious mammographic and/or clinical findings by performing ductal lavage on 200 patients prior to biopsy. Her team will then correlate cytopathologic findings with the biopsy pathology, with the goal of developing a less invasive way of making a breast cancer diagnosis and to decrease the number of breast biopsies. Progress Report: Findings from this research were published in Contemporary Diagnostic Radiology. 2003:26: 1-6. Researcher: Robert Chatterton, PhD, Professor, Departments of Obstetrics/Gynecology and Physiology, Northwestern University School of Medicine, Chicago, Illinois. Project: Nipple Aspirate Fluid Hormone and Response Parameters Award Amount: $15,000 Dr. Chatterton and his team have developed methods for separating nipple aspirate fluid (NAF) into three fractions for analysis of estradiol, its precursors, and certain products of estrogen responsive genes. For this research project, they will conduct these analyses in patients in which NAF is collected prior to ductal lavage. The aim is to relate the concentrations of DHEA, androstenedione, progesterone, IL-6, cathepsin D, estrone sulfate, and EGF to the presence of premalignant changes in cells obtained by ductal lavage. This work could lead new methods of early breast cancer detection. Researcher: Laurie Delmolino, PhD, Instructor, Tufts-New England Medical Center, Boston, Massachusetts. Project: The Feasibility of Gene and Protein Profiling of Normal Breast, Atypical, and Breast Cancer Cells from Ductal Lavage Award Amount: $5000 Final Report: Withdrawn Researcher: Christine Erdmann, PhD, and Georgianna Farren, MD, Lawrence Berkeley National Laboratory, Berkeley, California. Project: Female Breast Cancer and Environmental Risk Factors for Marin County—Pilot Study, Plus NAF Collection Component Award Amount: $5000 The breast cancer rate in Marin County, California, is the highest in the nation. The reason for this remains unclear. The community-based Marin Breast Cancer Watch, is conducting a look-back, case-control Adolescent Risk Factor Study to illuminate environmental factors that may be associated with increased breast cancer risk. Dr. Erdmann will investigate the influence of selected personal environmental exposures on female breast cancer risk during the ten-year period prior to diagnosis in women with breast cancer. She will compare these findings to those of women who do not have breast cancer. She will also assess the ability to perform NAF analyses in this type of research project. Findings from this study could identify modifiable personal environmental exposures that increase breast cancer risk.
Researcher: Laura Esserman, MD, MBA, Associate Professor Surgery, University of California, San Francisco.
Project: Detection of Telomerase Activity in Ductal Lavage and Ductoscopy Samples
Award Amount: $5,000
Telomerase, a cellular ribonucleoprotein enzyme synthesizes one strand of the essential telomeric DNA by copying a short template sequence within the RNA moiety of telomerase into telomeric DNA. Telomerase is often activated in immortalized human breast cancer cell lines, and in breast tumors. There is now good evidence that this activity helps cancer cells in their unbridled proliferation. Telomerase is much less active, or not active at all, in normal breast epithelium. Dr. Esserman and her team will perform ductal lavage and ductoscopy on ten patients with DCIS to assess the feasibility of obtaining cellular samples for telomerase assays. This work is an important step toward the development of targeted therapeutic interventions using telomerase for the treatment of premalignant breast conditions.
Researcher: Julian Kim, MD, Associate Professor, Cleveland Clinic Breast Center, Cleveland, Ohio.
Project: Genetic Analysis of Ductal Lavage Cells Using Fluorescence In-Situ Hybridization (FISH) and Molecular Fingerprinting Using Gene Chip Microarrays
Award Amount: $10,000
Molecular analysis of ductal lavage specimens using FISH or gene chip microarrays may provide useful prognostic information in addition to routine cytology. Dr. Kim and his colleagues are currently performing ductal lavage on high-risk patients and on patients with known breast cancer in the ipsilateral breast prior to lumpectomy. Dr. Kim’s study will test the hypothesis that genetic changes detectable either by FISH or gene chip microarray analysis may help to distinguish atypical cells associated with increased risk of breast cancer from atypical cells related to inflammatory or other benign proliferative breast disorders. Findings from this study may provide an objective method of evaluating ductal lavage specimens in addition to routine cytology. It could also lead to the development of new methods of following the progression of patients at high risk or the response of high-risk patients to chemopreventive agents.
Researcher: Bonnie King, PhD, Associate Research Scientist. Department of Therapeutic Radiology, Yale University, New Haven, Connecticut.
Project: Cytogenetic Analysis of Breast Touch Prep/Ductal Lavage Paired Cases
Award Amount: $10,000
Dr. King and her team will evaluate the correlation between cancer-associated abnormalities in breast lesions and exfoliated breast cells collected by ductal lavage by performing histopathologic, cytologic, and molecular cytogenetic analyses on paired cases of surgically excised breast lesions and ductal lavage specimens collected immediately before surgery.
Final Report: This study found that cytologic and genetic abnormalities associated with breast cancer progression can be detected in ductal lavage cells collected from women with in situ and invasive breast cancer and suggests that fluorescence in situ hybridization may have superior sensitivity and specificity compared with conventional cytology. Findings from this study were published in Clinical Cancer Research 2003 April; 9(4):1509-16.
Researcher: Gillian Mitchell, MD, Clinical Research Fellow, Cancer Genetics, Institute of Cancer Research, London, England.
Project: Developing Nipple Aspirate Fluid as a Method for Early Breast Cancer Detection in BRCA1/2 Germline Mutation Carriers.”
Award Amount: $10,000
This pilot project is designed to evaluate the constituents of nipple aspirate fluid (NAF) in premenopausal women with BRCA 1/2 mutations and the predictive value of NAF for detecting breast cancer. This project will provide the foundation for a multi-center serial NAF study.
Researcher: Nicholas Petrakis, MD, Professor Emeritus, Department of Epidemiology and Biostatistics. University of California, San Francisco.
Project: Birthplace and Neonatal Breast Hyerplasia in Chinese Infants.
Award Amount: $30,000
(Grant awarded in 1998)
Researcher: Jian Yu Rao, MD, Assistant Professor, Department of Pathology and Laboratory Medicine, University of California, Los Angeles.
Project: Molecular Mapping Analysis on Mastectomy Specimens
Award Amount: $10,000
Molecular mapping has the potential to validate the ductal lavage approach. Dr Rao will perform detailed molecular mapping of the ducts in five mastectomy breast specimens to compare the molecular map of the cancer-bearing duct with the noncancerous ducts. Known genes would be analyzed and new genes identified through molecular profiling to determine whether cellular and molecular signals—which could be used as surrogate markers for detecting breast lesions—could be detected in adjacent fields or duct systems. This research could lead to the development of new breast cancer detection and prevention techniques.
Researcher: Susan Troyan, MD, Surgical Director, BreastCare Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Project: Pilot Study of Ductal Lavage in Women with Microcalcifications on Mammogram
Award Amount: $15,000
Final Report: Withdrawn.
Researcher: Shawna Willey, MD, Chief of Breast Surgery, George Washington University Medical Center, Washington, DC.
Project: Expanded Use of Ductal Lavage to Patients with Previous Breast Cancer Treated with Breast-Conserving Surgery and Radiation
Award Amount: $10,000
Detecting a local recurrence in women who have previously been treated for breast cancer is difficult as surgical- and radiation-induced changes make mammography less sensitive. Dr. Wiley will perform ductal lavage on both breasts of 50 patients, using the contralateral breast that had not been radiated as a control to determine if ductal lavage is possible in the previously radiated breast, if adequate cellular material can be obtained, and if cytologic changes appear different in the radiated breast. Findings from this study could lead to new ways to detect a local cancer recurrence.
Researcher: Debrah Wirtzfield, MD, Assistant Professor, Surgery, Roswell Park Cancer Institute, Buffalo, New York.
Project: Assessment of Cells Harvested by Breast Ductal Lavage: Flow Cytometry and Microarray Analysis
Award Amount: $5,000
Final Report: Withdrawn
Researcher: Margaret Wrensch, PhD, Professor, Department of Neurological Surgery, University of California, San Francisco.
Project: Breast Fluid Tests for Early Breast Cancer Detection
Award Amount: $10,000
Grant awarded in 1999.
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