Researcher: Kimberly Baltzell, RN, PhD, Assistant Adjunct Professor, University of California, San Francisco.
Project: Oncogenic Viruses in Nipple Aspirate Fluid: Biomarkers for Breast Cancer Risk Assessment?
Award Amount: $5,000
Viruses have been found to cause several major human cancers. Recent studies have found that bovine leukemia virus (BLV), Epstein-Barr virus (EBV), and the human papilloma virus (HPV) are more frequently found in the breast tissues of women with breast cancer than in women with no history of the disease. Dr. Baltzell and her team intend to investigate whether it is feasible to use polymerase chain reaction (PCR) methods to detect these viruses in nipple aspirate fluid (NAF). They will also assess whether these viruses are more likely to be present in the NAF of women who have been diagnosed with breast cancer than in women with no history of the disease. The findings from this research could help lead to the development of a breast Pap smear for identifying women who are at high risk for breast cancer.
Researcher: Catherine Carpenter, PhD, Adjunct Assistant Professor, University of California, Los Angeles.
Project: Impact of Diet and Exercise Intervention on Breast Ductal Fluid Among Overweight to Obese Postmenopausal Women
Award Amount: $5,000
Obesity and adult weight gain increase the risk of developing breast cancer after menopause. Major mechanisms thought to be responsible for this increased risk include conversion of androstenedione into estrone by adipose tissue cells, promotion of inflammation, and enhanced production of growth factors. These obesity-related mechanisms may function locally at the breast, or systemically, or both. Dr. Carpenter and her team will assess whether relevant biomarkers, hormones, and growth factors contained in ductal fluid differ before and after a 12-week diet and exercise intervention. This study will shed light on the impact that weight change has on the breast.
Researcher: Richard Davies, MD, Chairman, Department of Surgery, Hackensack University Medical Center, and University of Medicine and Dentistry, New Jersey.
Project: Electronic Ductal Lavage as a Non-Invasive Technique to Identify Proliferative Changes and Altered Potassium Permeability Within the Ductal System of the Breast
Award Amount: $10,000
When a low frequency alternating current is passed across the nipple into the breast ductal system, and the voltage drop, phase shift, and capacitance is measured between a nipple sensor and skin surface electrodes, information can be obtained about the impedance properties of the ductal system as well as the integrity of the tight junctions between the epithelial cells. Dr. Davies and his team already have used this procedure, termed electronic ductal lavage, to identify increases in impedance associated with ductal hyperplasia and decreases in conductance associated with malignancy. They now intend use this procedure to assess whether ductal K-permeability is altered early in the development of breast cancer. This work could lead to the development of a new way to identify early stage pre-malignant breast cancers.
Researcher: James Going, PhD, Senior Lecturer and Consultant Pathologist, University of Glasgow Division of Cancer Science and Molecular Pathology, Scotland, UK.
Project: Resolving Paradoxes of Human Nipple Duct Anatomy
Award Amount: $10,000
No comprehensive, accurate data about duct anatomy in the nipple and in the breast currently exists. It is paradoxical that 5-9 major ducts can typically be cannulated and yield milk during lactation but that a cross section of the duct bundle in the papilla reveals 25 or more duct-like structures. Dr. Going and his team intend to use episcopic microscopy to generate high-resolution 3-D structural data on cancer removed via mastectomy to explore the hypothesis that there are a minority of "type A" ducts that open on the nipple and that correspond to true, milk-yielding ducts and a larger number of "type B" ducts that originate from skin appendages beneath the nipple surface and that make up most of the ducts in the duct bundle. By exploring the breast anatomy in this fashion, this work could lead to a better understanding of how to use the intraductal approach to diagnose and treat breast cancer.
Researcher: Jon Greif, DO, Surgeon, Carol Ann Read Breast Health Center, Alta Bates Summit Medical Center, Oakland, California.
Project: An Intraductal Approach to Breast Cancer Risk Assessment and Screening in a Diverse Population
Award Amount: $5,000
Standard breast cancer risk assessment tools, like the Gail model, were developed in research populations that consisted almost entirely of white women. Whether these tools are effective in determining breast cancer risk in non-white women is unproven. Dr. Greif and his team intend to conduct a prospective cohort study of asymptomatic women undergoing routine screening mammography at their Breast Health Center in Oakland, California, which is one of the most diverse cities in the United States. Women will have a Gail model risk assessment followed by nipple fluid aspiration and, when needed, ductal lavage. Women with cellular atypia will undergo diagnostic fuctoscopic examination with biopsy. The researchers will then assess which techniques proved most effective in determining breast cancer risk. This work will evaluate the acceptability of ductal lavage in a diverse community and provide information on which risk assessment tools are most effective in women of different racial and ethnic groups.
Researcher: Michael Hunerbein, MD, PhD, Department of Surgery and Surgical Oncology, Charite Campus Buch and Helios Hospital, Universitatsmedizin Berlin, Germany.
Project: Ductoscopic Biopsy and Ductoscopy Navigated Minimal Invasive Therapy of Intraductal Breast Lesions
Award Amount: $10,000
Fiberscopic ductoscopy is increasingly being used to evaluate intraductal pathology. Dr. Hunerbein and his team have developed a ductoscopic biopsy technique, called ductoscopic vacuum assisted biopsy, which allows targeted tissue sampling from intraductal breast lesions. They are now working to establish and evaluate the accuracy of a system for ductoscopically-guided navigation of instruments with optical tracking in mastectomy specimens. Their next step will be to test the procedure along with radiofrequency of intraductal lesions in women whose intraductal biopsies reveal a benign or prenoeoplastic histology. This work could lead to the development of procedures that help women with small preneoplastic intraductal lesions or nipple charge avoid major operations.
Researcher: Ferdinando Mannello, PhD, Institute of Histolngy and Laboratory Analysis, University of Urbino "Carlo Bo" Italy.
Project:Searching New Biomarkers in Nipple Aspirate Fluid: Peroxidation Status and Adhesive Molecules to Early Identify Breast Cancer
Award Amount: $7,500
In a research study funded in 2005 by the Dr. Susan Love Research Foundation, Dr. Mannello and his team found that nipple aspirate fluid (NAF) taken from women with breast cancer contains abnormal epithelial cells, ultrastructurally identified as biosyntheticallz active apocrine cells, that show interdigitated cytoplasmic protrusions on the cell surface and several zonula occludens. In contrast, NAF taken from women who do not have breast cancer has infrequently clustered epithelial cells linked mainly by zonulae adherens. The scientists also identified high levels and specific isoforms of proteolytic enzymes that may enhance the detachment of epithelial cells from the basal membrane into the NAF. Dr. Mannello intends to pursue these research findings by exploring the impact of lipid peroxidation on arachidonic acid and assessing whether peroxidation status can be used as a biomarker in NAF. This work could lead to the development of new methods for detecting the presence of cancer in NAF.
Researcher: Indira Poola, PhD, Research Professor, Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC.
Project: MMP-1 and CEACAM6 Expression in Ductal Lavage Cells to Predict Breast Cancer Development
Award Amount: $15,000
Dr. Poola and her team used global gene expression analysis to identify and validate two breast cancer predictive molecular markers, MMP-1 and CEACAMG, in women with atypical ductal hyperplasia. They have also demonstrated the feasibility of detecting MMP-1 mRNA by Q real-time PCR in a small number of ductal lavage samples. Dr. Poola and her team intend to use a larger numaer of ductal lavage samples to determine the minimum number of cells/cDNA required to detect each marker; to assess whether marker expression is indeed more prevalent in atypical cells than in benign cells; and to examine whether there is a correlation between the presence of these markers and known breast cancer risk factors. This work could lead to the development of a breast Pap smear that could detect precancers in the breast before they have become mammographically detectable.
Researcher: Santosh Kumar Somasundaram Research Fellow, Royal Free and University College Medical School, University College London, UK.
Project: Elastic Scattering Spectroscopy and Photodynamic Therapy for Diagnosis and Treatment of Ductoscopic Abnormalities.
Award Amount: $7,500
Elastic Scattering Spectroscopy (ESS) is an optical technique used to analyze the absorption and scattering of incident broadband white light by the cellular and subcellular components of tissue. By correlating ESS spectra with conventional histology, an algorithm can be developed that can differentiate between benign and malignant tissue. Photodynamic therapy (PDT) is a new, non-thermal technique that allows the local ablation of tissue by delivering a photosensitizing drug and light through a ductoscope. Mr. Somasundaram and his team intend to evaluate whether ESS can be used to diagnose the nature and extent of precancerous tissue seen through ductoscopy and if PDT can be used to treat these early intraduatal breast cancers. This work could lead to the development of a new method for treating localized ductal carcinoma in situ (DCIS).
Researcher: Atilla Soran, MD, Professor of Surgery, Magee Women's Hospital of University of Pittsburgh Medical Center, Pittsburg, PA.
Project: Evaluation of Anti-Cyclin B1 Antibodies in Nipple Aspirate Fluid
Award Amount: $5,000
NAF is a potential source of biomarkers for early diagnosis or risk assessment of breast cancer. Cyclin B1 is an important molecule involved in the transition from G2-to-M phase of the normal cell cycle. In cancer cells, cyclin B1is overexpressed throughout the cell cycle and resides primarily in the cytoplasm. Patients with cyclin B1 overexpressing tumors have antibodies and T cells specific for various epitopes of this molecule. Dr. Soran and his team intend to compare the level of anti-cyclin B1 found in the NAF and blood of women with breast cancer, women with premalignant lesions, and healthy women. They also intend to evaluate whether there is a correlation between cyclin B1 antigen expression in pathology specimens of women with breast cancer and premalignant disease. This work could lead to the development of a breast Pap smear that can detect cancer and premalignant lesions earlier than is currently possible with conventional diagnostic methods.
Researcher: Debra Strick, Doctoral Candidate, University of California, Los Angeles.
Project: Intraductal Micro Magnetic Resonanae Imaging and Spectroscopy
Award Amount: $10,000
Current imaging techniques can detect suspected tumors that are as small as 1 mm. Ms. Strick and her team are working to develop an intraductal magnetic resonance probe that could be used in the human mammary ducts to identify sub-millimeter tumors. If successfully developed, these micro-scale images of the mammary ducts, which could be used concurrently with ductal lavage and biopsy, might be used to facilitate research and treatment plannimg by providing microscopic imaging of the epithelial cells as well as high-precision localization of tumors and tumor margins.
Researcher: Susan Sturgeon, PhD, Associate Professor, University of Massachusetts Amherst School of Public Health and Health Sciences.
Project: Effects of Flaxseed on Nipple Aspirate Fluid Levels of Biomarkers of Breast Cancer Risk
Award Amount: $10,000
Phytoestrogens are structurally similar to mammalian estrogens, which allows them to bind weakly to estrogen receptors. Plant lignans are the principal source of phytoestrogens in individuals who do not consume soy foods and flaxseed is the richest dietary source of lignans. By inhibiting the activity of aromatase involved in the conversion of androgens to estrogens, flaxseed lignans may reduce circulating levels of certain estrogens that have been associated with breast cancer risk. Dr. Sturgeon and her team intend to establish the feasibility of collecting nipple aspirate fluid (NAF) in a dietary intervention study of flaxseed in overweight/obese postmenopausal women. NAF will be collected at the beginning and end of the 12-week intervention, and the levels of hormones linked with breast cancer found in the NAF analyzed. This research will advance our understanding of whether phytoestrogens alter breast cancer risk.
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