Recent WAR-funded Research Projects

Women At Risk

A vital part of WAR's mission is to enhance the lives of women through funding innovative breast cancer research projects. Over the past several years, WAR has awarded grants to thirty-nine breast cancer pilot studies that cover a broad range of topics including surgery, oncology, radiology, laboratory, epidemiology, genetics, and complementary/ alternative medicine. WAR's research grants are dedicated to better understanding the complex causes of breast cancer and developing new methods for prevention, early intervention, and effective treatment.

2010

Micro-RNA fingerprint discovery for breast cancer

Sheldon Feldman, M.D., Chief Surgeon, Comprehensive Breast Center, NewYork-Presbyterian Hospital/ Columbia University Medical Center, Vivian L. Milstein Associate Professor of Clinical Surgery, Columbia University College of Physicians & Surgeons

The purpose of this study is to identify unique microRNA fingerprints in patients undergoing breast cancer surgery. This would be the first step in developing a screening test for breast cancer that is a minimally invasive blood test similar to the PSA (prostate specific antigen) for prostate cancer. A blood screening test such as this would allow for more widespread breast cancer screening as well as the ability to accurately monitor the efficacy of treatment. The microRNAs being examined in this study have recently been identified as breast cancer tumor suppressors or oncogenes, and may show promise in the early detection of breast cancer. To assess the feasibility of microRNA as a biomarker for breast cancer development, samples of blood, breast tissue and nipple fluid will be assessed and compared in order to identify the microRNA fingerprint for breast cancer.

Pre-Surgical Evaluation of MK-2206 in Patients with Operable Breast Cancer

Kevin Kalinsky, M.D., Assistant Professor of Clinical Medicine, Columbia University College of Physicans & Surgeons

The P13K/Akt signaling pathway is an important pathway in breast tumor biology. At the cellular level, the pathway has multiple functions, including aiding in breast cancer growth and spread. As a result, significant research has focused on the development of new drugs that target this pathway, with the hopes of impeding breast cancer growth. MK-2206 is a novel agent that specifically targets Akt and has shown efficacy in the pre-clinical setting, as well as in an early-phase clinical trial. The goal of this pre-surgical study is to learn more about the drug and how it impacts breast cancer cells, while at the same time exposing patients to a limited duration of treatment. The information learned from this study will be directly used to design and plan future studies with MK-2206 as well as the increasing number of drugs in development to target the PI3K/Akt pathway.

Breast Density, Change in Breast Density and Breast Cancer Risk in a Population at High-Risk for Breast Cancer

Merry Beth Terry, Ph.D., M.A., Associate Professor of Epidemiology, Columbia University Mailman School of Public Health

Breast density is a strong and potentially modifiable risk factor for breast cancer. Epidemiologic studies have consistently supported a four to six-fold increase in breast cancer incidence for women with dense breast tissue for up to ten years following breast density assessment. Few studies have examined longitudinal change in breast density and factors associated with these trends, particularly in a population of women at high risk for breast cancer. This study will contribute to the current knowledge of breast cancer etiology by measuring initial breast density scores, as well as within-individual changes in breast density and factors that are related to these changes, in a high-risk population. Given that breast density is modifiable, reductions in breast density may reduce breast cancer risk, and identifying factors that influence changes in breast density over time could provide crucial knowledge for interventions to reduce breast cancer incidence.

Use of Urinary Biomarkers for Detecting Drug Adherence with Aromatase Inhibitors in Women with Early Stage Breast Cancer

Alfred Neugut, M.D., Ph.D., M.P.H., Professor of Medicine, Columbia University College of Physicans & Surgeons, Professor of Epidemiology, Columbia University Mailman School of Public Health

Adjuvant chemotherapy and hormonal therapy have had a major impact on mortality for women with non-metastatic breast cancer. It is thus surprising to learn that a substantial fraction of women do not complete their adjuvant therapy, and that if they do not complete it, they lose much of the survival benefits of the therapy. To track adherence of hormonal therapy, this study will measure drug levels of urine metabolites; this method has not been used in any oncology trial to date. The aims are to determine the rate of non-adherence as detected by urine AI biomarker analysis and to determine the number of days it takes from discontinuation of AI to the time a urine biomarker test is no longer able to detect metabolites in the urine. This information is critical for determining the appropriate power for an intervention as well as the utility and feasibility of this biomarker for detecting adherence rates in the community.

2009

Chemopreventive and Anticancer Potential of Vitamin D And Rosemary on Breast Cancer
Linda S. Einbond, PhD, Associate Research Scientist, Department of Rehabilitation Medicine, Columbia University College of Physicians & Surgeons

Although chemopreventive agents aid in the reduction of risk for developing breast cancer, they are limited by their effectiveness among certain subsets of women and their unwanted toxicities. Women who lack estrogen and progesterone receptors as well as HER2 amplification, those with "triple negative" tumors, do not benefit from using these existing hormonal therapies. Literature suggests that vitamin D may have a protective effect against the development of breast cancer. However, high doses of vitamin D have also been associated with unwanted side effects such as increased levels of calcium in the blood. Rosemary contains carnosic acid, which is believed to have the ability to not only enhance the anti-cancer effects of vitamin D, but also to inhibit the growth of estrogen-receptor-negative breast cancer. The aim of this study is to compare the effects of calcitrol (a form of vitamin D) and rosemary/carnosic alone and in combination on the proliferation of normal mammary epithelial cells as well as in triple negative breast cancer cell lines. A second aim is to examine the specific signaling pathways and cellular targets involved in the actions of calcitrol and carnosic acid. Findings from this study could elucidate how to utilize vitamin D as a chemopreventive agent while avoiding the unwanted side effects caused by high doses of vitamin D.

Exploiting the Mutant P53 and Mutant Brca Status In Transgenic Breast Cancer Models
Robert L. Fine, MD, Associate Professor of Medicine, Division of Hematology/Oncology, Columbia University College of Physicians & Surgeons

BRCA1 tumors have distinct gene expression profiles and are classified as "triple negatives." This means that they are negative for estrogen and progesterone receptors as well as HER2 amplification. Treatment options for patients with basal-like breast cancer, "triple negative" tumors, are limited, and prognosis is poor. Mutant p53 is also expressed at higher levels in human breast cancer cases. It is approximated that 80-85% of BRCA1 and BRCA2 tumors express mutant p53. Recently, mice models were created which bear a resemblance to basal-like breast carcinoma by altering the BRCA1 and BARD1 genes. This study proposes to utilize the new genetically modified mice models to examine new therapeutic biologics and chemicals that are designed to target pathways, which are commonly mutated in human breast cancer cases. More specifically it is hypothesized that by utilizing p53 tetrapetide and cross-linking alkylators, p53 function could be restored. Findings from this study could potentially impact not only breast cancer treatment but also breast cancer prevention strategies as well.

Chromosome 17 Telomere Length and Breast Cancer Risk
Jing Shen, PhD, Assistant Professor of Clinical, Department of Environmental Health Sciences, Columbia University Mailman School of Public Health

All humans have 23 pairs of chromosomes, which compose our genetic make-up. Telomeres are composed of a large number of tandem repeats, which are located at the ends of our chromosomes. Each cell cycle, telomere length decreases by roughly 20-200 base pairs. Several important breast cancer genes (e.g. BRCA1, HER2) are located on one particular chromosome, chromosome 17. Both chromosomes 17p (short arm) and 17q (long arm) also have shorter telomeres compared to other chromosomes. The study will examine if shortened telomere lengths in chromosomes 17p and 17q individually are associated with increased breast cancer risk. Whether the telomere lengths of these chromosomes are modified by smoking, body mass index, menopausal status and global telomere length to affect the risk of developing breast cancer will also be examined. Potential findings from this study could impact breast cancer prevention strategies.

Genetic Synthetic Lethality: Genetics Approaches for Personalized Breast Cancer Therapy
Jose M. Silva, PhD, Assistant Professor of Pathology, Department of Pathology & Cell Biology, Institute for Cancer Genetics/Irving Cancer Research Center, Columbia University College of Physicians & Surgeons

Newer cancer therapies have been designed with the goal of reducing the toxicity of their classical counterparts, while also creating more individualized treatment plans. It is believed that genetic synthetic lethal interactions can be utilized to identify new targets for the development of these more personalized therapies. Genetic synthetic lethal interactions happen when two individually innocuous appearing genetic alterations work in tandem to inhibit cell growth. The theory is that these interactions can be utilized to find which genes limit viability of tumor cells that carry specific genetic lesions. This study aims to identify genes that show synthetic lethality with major breast cancer alterations in vitro (utilizing a 3D model of breast acici morphogenesis) and subsequently confirm these results in vivo (using a mosaic mouse model of breast tumorigenesis). This study could potentially significantly impact the creation of new, more individualized breast cancer therapies.

2008

Mammography Screening and Satisfaction with Health Care Among Latina Women
Ana Abraido-Lanza, PhD, Associate Professor of Sociomedical Sciences, Department of Sociomedical Sciences, Columbia University Mailman School of Public Health

Despite growing interest in cancer-related disparities and access to health care, relatively little is known about different aspects of care among Latinas, their satisfaction with the care they receive, the predictors of satisfaction, and whether these variables influence women's screening practices. This study will examine whether various access to health care factors predict satisfaction with health care and utilization of mammography screening among Latina women from the Dominican Republic living in New York City. The potential outcomes and benefits of the study are to identify the most important predictors of screening, which can be used to inform health interventions and health care policies that address disparities in breast cancer between Latinas and non-Latinas.

Phytoestrogens And Breast Cancer Prevention: Mechanisms Of Action
Hari K. Bhat, PhD, Assistant Professor of Environmental Health Sciences, Columbia University Mailman School of Public Health

Phytoestrogens are a class of plant-derived compounds that are structurally similar to estrogens. Studies have shown that dietary factors, particularly phytoestrogens, may inhibit cancer growth. We hypothesize that phytoestrogens exert their chemoprotective effects against breast cancer by shifting estrogen metabolic pathways, reducing oxidative stress and altering breast development. We will use animal models of breast cancer to analyze the role of phytoestrogens in estrogen metabolism and determine whether phytoestrogens can prevent estrogen-induced breast tumors. The long-term goal of our study is to suggest the use of specific phytoestrogens for the chemoprevention of breast cancer. The successful completion of the proposed study would provide innovative new ideas for breast cancer prevention strategies.

Quantitative Ultrasound Study Of Radiation-Induced Normal Tissue Toxicity In Breast
Tian Liu, PhD, Assistant Professor of Medical Physics, Department of Radiation Oncology, Columbia University College of Physicians & Surgeons

Breast-conservation surgery in combination with radiation therapy is an effective treatment for women with early stage breast cancer. Radiation therapy reduces recurrence and prevents development of additional breast tumors. However, efficacy of radiation treatment is limited by radiation injury to normal tissue. Currently there is no objective means of measuring breast tissue injury/toxicity in the clinical setting. Ultrasound is safe and cost-effective imaging modality. This proposed study is the first clinical application of a novel, non-invasive and quantitative ultrasound-based technique to examine acute and late radiation toxicity in the breast.

HMGA2 Expression And Breast Cancer
Jeanine D'Armiento, MD, PhD, Associate Professor of Medicine, Division of Molecular Medicine, Columbia University College of Physicians & Surgeons

Recent studies have identified a molecular marker for breast cancer, HMGA2, which appears to have a role in tumor progression and metastasis. Interestingly, HMGA2 has not been identified in healthy patients. Further studies have shown that HMGA2 mRNA expression in the blood of breast cancer patients correlates with poorer survival and can be a better predictor of survival than even lymph node metastasis. We hypothesize that in patients with locally advanced and metastatic breast cancer, HMGA2 expression can be an important predictor of clinical response to treatment. Our aim is to compare HMGA2 expression at the protein level in tissue samples using a novel technique (ELISA) in the peripheral blood of cancer patients to determine the feasibility of its use in prognosis and clinical management.