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Recent WAR-funded Research Projects

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.

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.

2007

Psychosocial Approaches To Participation In Breast Cancer Genetic Assessment Programs Among African American Women
Sherri Sheinfeld Gorin, PhD, Research Associate Professor of Health Education, Department of Health & Behavior Studies, Columbia University

There are currently no established psychosocial protocols to address the needs of the African American women in familial risk programs. This study is a two-arm randomized clinical trial, assigning African American women who are first degree relatives of those diagnosed with breast cancer at random to either a 1) Culturally-Tailored Cognitive-Affective-Social Network Intervention (CT-CASN); or 2) a General Health Education Group as a control. The proposed intervention (CT-CASN) is culturally tailored to African American women to systematically counsel individuals about the cognitive, affective, and social network barriers they are likely to experience with regard to breast cancer genetic susceptibility programs.

Long-Term Neurotoxicity In Breast Cancer Patients Treated With Taxane-Based Chemotherapy
Dawn Hershman, MS, MD, Florence Irving Assistant Professor of Medicine and Epidemiology, Co-Director, Breast Program, Herbert Irving Cancer Center, Columbia University Medical Center

The purpose of this study is to evaluate the long-term prevalence, severity, and natural history of neuropathy induced by taxanes in breast cancer patients. A greater understanding of factors which may predispose to the development of taxane-induced peripheral neuropathy may lead to interventions to treat and prevent this therapy-related side effect.

Pilot Biomarker Modulation Study Of Vitamin D In Premenopausal Women At High Risk For Breast Cancer
Katherine D. Crew, MD, MS, Assistant Professor of Medicine and Epidemiology, Columbia University College of Physicians & Surgeons, Division of Oncology, Columbia University Medical Center

Several studies suggest that vitamin D may influence breast cancer development, which has resulted in increased interest in the use of vitamin D for the treatment and prevention of breast cancer. The purpose of this trial is to determine the biological effects of a one-year intervention of vitamin D on biomarkers of breast cancer risk. The results of this pilot study will be used to implement a larger multicenter trial of vitamin D for breast cancer chemoprevention.

Hybrid Breast Implants From Stem Cells And Biomaterials
Eduardo K. Moioli, PhD, Postdoctoral Research Scientist, College of Dental Medicine, Columbia University Medical Center

Current methods for breast implants rely either on artificial materials such as silicone gel filled and saline filled implants or tissue flaps obtained from other parts of the body such as muscle, fat and skin. All these procedures are associated with certain risks and complications. This study proposes to explore current technologies that have been developed to regenerate fat tissue from stem cells, which may be used as a natural implant material for reconstruction of the breast, avoiding the common complications associated with artificial breast implants (allergic and foreign body reactions) and tissue flaps (lack of tissue donor site, donor site scarring, and tissue flap death). Stem cells have the potential to revolutionize medical practice, providing skillful doctors and surgeons with better alternatives for effective treatments. The results obtained here will serve as valuable preliminary data for larger scale grant proposals for the further development of stem cell based breast implants and future transition from the research laboratory to bedside treatments.

Research Using Data from the Women At Risk (WAR) High-Risk Registry

Breast Cancer Risk Factors In Young Women
Ben Pocock, MD, Jennifer Chun, MPH, Kathie-Ann Joseph, MD, MPH, Laura Klein, MD, Mahmoud El-Tamer, MD, Freya Schnabel, MD, Department of Surgery, Columbia University Comprehensive Breast Center, Women At Risk, New York Presbyterian Hospital, Columbia University Medical Center

This study queried the Registry for women ≤35 years to determine the significance of established risk factors over time in a population of high-risk younger women. High-risk was defined as having one or more of the following: a strong family history of breast cancer (FHBC), a biopsy-proven history of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). Descriptive analyses were used to look at these factors over time and to compare women with and without breast cancer. Out of 1412 high-risk women, 199 were identified as ≤35 years of age with a median follow-up of 4 years. The median age was 32 years (range 15-35 years). 178 (89%) women had a strong FHBC, 21 (11%) had ADH, 5 (3%) had ALH and 12 (6%) had LCIS. Only 3 (1.5%) developed breast cancer during the study period; all of these 3 cases had a strong FHBC and none had a prior high-risk lesion. Patients who had high-risk lesions but no FHBC did not develop breast cancer during this follow-up period. In conclusion, being ≤35 years of age and having a strong family history of breast cancer appeared to be associated with the development of breast cancer, while other well-established histologic risk factors were not. Therefore, ADH, ALH, and LCIS may have different prognostic significance in young women. These findings help us to better understand risk factors in this group of younger women and may aid in the evolution of defining age-appropriate risk management and strategies.

Results of the study were presented at the 24th Annual Miami Breast Cancer Conference in Miami, FL.

The Interaction Of Increasing Age And Breast Cancer Risk Factors
Jennifer Chun, MPH, Ben Pocock, MD, Kathie-Ann Joseph, MD, MPH, Laura Klein, MD, Mahmoud El-Tamer, MD, Freya Schnabel, MD, Department of Surgery, Columbia University Comprehensive Breast Center, Women At Risk, New York Presbyterian Hospital, Columbia University Medical Center

Currently, there is no information on how risk factors predict breast cancer incidence in women who are ≥70 years of age. This study explored the impact of known risk factors on high-risk women 70 years of age or older. Out of 1412 women in the WAR Registry, 82 women were ≥70 years of age (range 70-91). Twenty had a history of ADH (24%), 5 had ALH (6%), 27 had LCIS (33%), and 52 women had FHBC (63%). With a mean follow-up of 4 years, 6 of these women developed breast cancer (7.3%). The mean Gail score for the ≥70 age group was 4.3, as compared to 4.7 in the subset with cancer. Of the 6 breast cancer cases, two patients presented with DCIS. The remaining four were stage I at diagnosis. All tumors were low-grade with positive estrogen receptors. The Fisher's exact tests demonstrated that ADH (p=0.15), ALH (p=1.0), LCIS (p=0.66), and FHBC (p=0.62) were not statistically significant predictors of breast cancer within this age group of high-risk women. Preliminary data on high-risk women who are ≥70 years indicate that having a history of ADH, ALH, LCIS and FHBC were not strong predictors of breast cancer in this population. These findings contribute to a better understanding of the interaction of established risk factors and age. This study also emphasizes the importance of defining age-appropriate recommendations for breast cancer risk management, including surveillance and chemoprevention, for women who are 70 years of age or older. Results of the study were presented at the 31st Annual Symposium of the American Society of Breast Disease in San Francisco, CA.

2006

Identification Of Genetic Modifiers Of Brca1 Or Brca2 In Ashkenazi Mutation Carriers
Wendy K. Chung, MD, PhD, Herbert Irving Assistant Professor of Pediatrics in Medicine, Columbia University College of Physicians and Surgeons, Director of Clinical Genetics and Clinical Oncogenetics, Division of Molecular Genetics, Columbia University Medical Center

Three common founder mutations in BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) account for over 98% of mutations in BRCA1 and BRCA2 in the Ashkenazi population. There are likely genetic variations that modify the risk of cancer in BRCA1 and BRCA2 carriers. The purpose of this study is to determine whether these genetic variants (CHEK2, MSH2, P53, RAD51, MTHFR, and APC) are associated with developing breast cancer. This study may improve our ability to stratify cancer risk for BRCA1 and BRCA2 mutation carriers and individualize plans for prevention and treatment of breast cancer.

The Role Of Notch In The Phenotypic Switch From Ductal Carcinoma In Situ (Dcis) To Invasive Carcinoma Of The Breast
Nikki M. Feirt, MD, Assistant Professor of Clinical Pathology, Columbia University College of Physicians and Surgeons

Research has shown that the Notch gene plays an important role in cell survival, cellular proliferation, and differentiation. The purpose of this study is to determine whether Notch plays a direct role in regulating the switch from in situ to invasive carcinoma. The findings of this study will increase our knowledge of tumor progression, invasive and subsequent metastatic disease, and may define new targets for cancer therapeutics.

Quantitative Assessment Of Tissue Toxicity In Ultrasonic Tissue Characterization Imaging
Tian Liu, PhD, Assistant Professor of Medical Physics, Department of Radiation Oncology, Columbia University College of Physicians & Surgeons

For women with early stage breast cancer, breast-conservation surgery in combination with radiation therapy is an effective treatment. However, there is currently no objective means of measuring breast tissue injury or toxicity of radiation therapy in a clinical setting. This proposed study is the first application of a novel, non-invasive and quantitative ultrasound-based technique to examine acute and late radiation toxicity in the breast. Recent studies suggest that African-American patients have a higher likelihood of developing radiation toxicity in comparison to Caucasian patients. In this pilot study, we will also investigate the relationship between toxicity and race.

Effects Of Physical Activity And Dietary Change In Minority Breast Cancer Survivors
Heather Greenlee, ND, MPH, Postdoctoral Research Scientist, Department of Epidemiology, Columbia University Mailman School of Public Health

Hispanic and African-American breast cancer survivors are more likely to be obese and sedentary compared to non-Hispanic white women, yet there are few studies on obesity, exercise, dietary change, and cancer risk among these high-risk ethnic groups. This pilot study proposes to examine the effects of an exercise and dietary change program (at neighborhood Curves locations) on weight reduction and biological markers associated with breast cancer risk in breast cancer survivors from an ethnic minority urban population.

Telomere Shortening, Oxidative Damage And Breast Cancer Risk
Jing Shen, PhD, Associate Research Scientist, Department of Environmental Health Sciences, Columbia University Mailman School of Public Health

Telomeres are specialized DNA-protein structures that consist of a large number of repeat sequences at the ends of chromosomes. Telomere shortening can lead to genomic instability that in turn drives the tumor formation process in pre-malignant breast lesions and normal breast tissues. The goal of this study is to look at the potential modifying effects of oxidative damage and antioxidant capacity on telomere shortening and breast cancer risk. The findings of this study can have important implications for improved preventive, diagnostic and treatment strategies for breast cancer.

Visualizing The Influence Of Brca2 On The Assembly Of Rad51 Nucleoprotein Filaments During Dna Repair
Eric C. Greene, PhD, Assistant Professor of Biochemistry & Molecular Biophysics, Columbia University College of Physicians & Surgeons

This research study will focus on understanding the molecular nature of DNA repair mechanisms that are involved in critical cellular processes including the behavior of BRCA2 and Rad51 as they interact with individual DNA molecules. The investigators of this study will employ a novel approach with fluorescence, using an ultra-sensitive optical microscope that can potentially monitor the progress of a single DNA repair reaction in vitro with sub-second temporal resolution. The findings of this research will contribute to our knowledge of aberrant DNA repair systems, molecules of DNA, and determine whether BRCA2 can directly assemble to correct sites on the individual DNA molecules.