Researcher: Patricia Berg, PhD, Associate Professor, Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC.
Project: Expression of BP1 in Ductal Lavage Samples from Women at Risk for Breast Cancer Award Amount: $10,000
Dr. Berg's group has discovered and cloned a new potential oncogene called BP1. Their previous research has found high levels of BP1 in breast tumors, as compared with normal tissue. In addition, all ER-negative tumors they tested were BP1-positive, while BP1 was overexpressed in the tumors of 89 percent of African-American women, compared with 57 percent of Caucasian women. BP1 expression also was found to correlate with the aggressiveness of breast cancer. Based on these findings, BP1 has the potential to be a useful biomarker for breast cancer risk assessment, especially for African American women. This study will examine and compare ductal lavage fluid from normal and high-risk African American and Caucasian women to assess the utility of BP1 as a marker for risk using ductal lavage.
Researcher: Regina Brown, MD, Medical Oncology Fellow, Hematology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Project: The Feasibility and Safety of Intraductal Administration of Pegylated Liposomal Doxorubicin (Doxil) in Women
Award Amount: $10,000
Dr. Brown's group previously demonstrated that administration of Doxil into the mammary ducts of HER2/transgenic mice was associated with tumor regression that is equivalent to or superior to that seen with intravenous administration, but without systemic toxicity. This phase I clinical trial will explore the feasibility, safety, and maximum tolerated dose of Doxil administered in to one nipple aspirate fluid-producing duct in women with breast cancer awaiting mastectomy. The researchers will also evaluate the concentrations of Doxil in plasma and in breast tissue at the time of mastectomy and assess the feasibility of obtaining baseline and post-therapy measurements of candidate markers that may be used in future trials to predict activity of intraductal therapy. This study is a critical step toward optimizing the intraductal route for administration of agents that can eradicate pre-malignant or non-invasive ductal lesions, thereby preventing breast cancer from occurring.
Researcher: Scott L. Kominsky, PhD, Assistant Professor, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Project: Intraductal Nano-Polymer Drug Delivery for Breast Cancer Prevention and Therapy
Award Amount: $10,000
Dr. Kominsky's laboratory has been exploring the use of biodegradable polymer non-spheres for drug delivery in the mammary ductal network. These delivery systems greatly increase drug half-life, providing a slow and sustained release of drug over days to years. This study will explore whether CPE-loaded biodegradable polymer nano-spheres delivered with or without Doxil by intraductal injection can prevent breast tumor formation in rats. CPE (clostridium perfringens enterotoxin) is a novel drug that elicits rapid and specific cell lysis of cells expressing its receptors, Claudin (CLDN)-3 and –4. Dr. Kominsky previously found that CLDN-3 and –4 are overexpressed in breast cancer. This study could lead to the production of a novel breast cancer drug capable of sustained drug delivery over extended periods of time, reducing the need for repeated drug administration.
Researcher: Ferdinando Mannello, PhD, Associate Professor, Institute of Histology and Laboratory Analysis, University "Carlo Bo" of Urbino, Urbino, Italy.
Project: Bio-Molecular Characterization and Cytometric Evaluation of Nipple Aspirate Fluids to Identify Bio-Markers of Breast Cancer
Award Amount: $10,000
Dr. Manello's group has previously described biochemical profile and ultrastructural features of cellular components in subtypes of nipple aspirate fluid (NAF) that are related to an increased risk of breast cancer. This study will use biochemical, molecular, and cytometric approaches to identify cellular and biochemical markers in NAF collected from healthy women, women with benign breast disease, and women with breast cancer. These markers will also be evaluated in vitro in hormone-dependent and -independent breast cancer cell lines. Identifying these bio-markers in NAF could lead to new methods of assessing which women are at high risk for developing breast cancer.
Researcher: Gertraud Maskarinec, MD, PhD, Associate Professor, Cancer Research Center of Hawaii, University of Hawaii, Honolulu.
Project: Short-Term Effects of Soy on Estrogens and Breast Cell Proliferation in Nipple Aspirate Fluid
Award Amount: $10,000
Epidemiologic and experimental studies support a protective effect of dietary soy against breast cancer, but how it may do so is not well understood. Because estrogen levels in serum are poorly correlated with concentrations in breast tissue, measurements in NAF may be an appropriate approach to detect changes due to soy exposure directly in the breast. This pilot study will examine the possible short-term effect of two daily servings of soy on estrogen levels in NAF among premenopausal women at high risk for breast cancer, evaluate the cytologic characteristics of epithelial breast cells from NAF during periods of varying soy exposure, and measure isoflavone concentrations in NAF during no soy intake and high soy intake periods. Findings from this study will advance our understanding of the relationship between soy intake and breast cancer risk.
Researcher: Brian K. Petroff, DVM, PhD, Assistant Professor, Department of Internal Medicine, Breast Cancer Prevention Center, University of Kansas Medical Center, Kansas City.
Project: Laser Capture Microdissection and Real Time Polymerase Chain Reaction to Assess Breast Biomarker Gene Expression Following Random Periareolar Fine Needle Aspiration and Ductal Lavage
Award Amount: $10,000
In conjunction with the company Arcturus, Dr. Petroff's team has developed a method of performing quantitative real time polymerase chain reaction (qRT-PCR) using cDNA from modified Cytolyt-fixed random periareolar fine needle aspiration (RPFNA) cytology samples that have undergone laser capture microdissection. This pilot study will assess the feasibility of using these qRT-PCR techniques on ductal lavage samples. The study will assess RNA and cDNA yields and gene expression as measured by qRT-PCR. In addition, the team will measure the relative and absolute gene expression for COX-2, ER, PGR, pS2, VEGF, survivin and several proliferation markers plus housekeeping control genes. If successful, this study would provide the basic developmental work for the performance of multiple qRT-PCR assays on a modest number of cells harvested by RFPNA and DL.
Researcher: Edna K. Valdes, MD, Fellow, Surgical Oncology, Beth Israel Medical Center, New York, New York.
Project: Is Persistent Nipple Aspirate Fluid in Women on Tamoxifen Prognostic for Adverse Breast Events?
Award Amount: $ 5,000
Clinicians have observed that high-risk women on tamoxifen are less likely to produce NAF. If this is because tamoxifen inhibits NAF production, it could mean that women who continue to produce NAF while on tamoxifen are at higher risk for developing breast cancer and are resistant to tamoxifen. Dr. Valdes intends to conduct a prospective study of high-risk women (newly diagnosed with breast cancer or LCIS or BRCA 1/2 positive). The women will be screened for NAF production at the start of the study. The study group will be started on tamoxifen; the control group will comprise women who decline tamoxifen and those who are hormone receptor negative. The women in both groups will be screened for NAF production every six months. This study has the potential to confirm the observation that NAF production while on tamoxifen is an indicator of greater risk and tamoxifen resistance.
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