Medicine and Health Sciences Commons^™

Assessing Identification Of Newly Diagnosed Breast Cancer Patients For Referral To Genetic Counseling, Corinne Marie Locke

Theses and Dissertations

Since 1998, the National Comprehensive Cancer Network (NCCN) guidelines have specified clinical indications for genetic testing for breast cancer susceptibility genes, but retrospective studies have shown that, despite meeting the NCCN criteria, patients are not always advised of the option of genetic testing. Further compounding this issue, studies have shown that cancer family history intake and documented family history can be incomplete even when taken by oncology providers. At this study site and other cancer centers in the country, patients with a new diagnosis of breast cancer are referred for genetic counseling by their cancer care team if they are …

Exosomal Mirnas As Biomarkers For Radiation Toxicity In Breast Cancer Patients, Mina V. Mcginn

Theses and Dissertations

Radiotherapy (RT) is a standard treatment for most breast cancer patients (BCPs), but is often accompanied by acute and late toxic effects in normal tissue. Exosomes are nano vesicles about 30-150nm in size that originate from the endosomal network and are found in most body fluids. Exosomes are a fundamental driver of intercellular communication by transferring proteins, lipids and microRNA (miRNA). Exosomal miRNA (Exo-miRNA) signatures may serve as non-invasive prediction biomarkers of post-radiation toxicities of BCPs. Eighty six BCPs treated in the Radiation Oncology Department were enrolled in an IRB approved study. BCPs were evaluated weekly during RT and at …

Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock

Theses and Dissertations

The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …

Life Course Health Effects Of Early Life Trauma, Jennifer Mei Ping Woo

Theses and Dissertations

The experience of trauma and psychosocial stress over the life course can have lasting impacts on health. Childhood and adolescence may serve as a particularly sensitive period during which trauma may become biologically embedded and affect adult health. Evaluating the pathways through which early life trauma can affect biological mechanisms of disease development provides insight into the early origins and etiology of adverse health outcomes in adulthood and provides potential targets to help mitigate their effects.

Using data from the Sister Study, a large prospective cohort study of women residing in the U.S. or Puerto Rico aged 35 to 74 …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Dietary Advanced Glycation End-Products (Ages) And Breast Cancer Risk And Survival, Omonefe Opeyemi Omofuma

Theses and Dissertations

Introduction: Advanced glycation end-products (AGEs) are implicated in the pathogenesis of chronic diseases including cancer. AGEs are produced endogenously and are also consumed from foods. High amounts of AGEs are found in animal products and processed foods, and AGE formation is accelerated during cooking at high temperatures. Using data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), we assigned and quantified NƐ-carboxymethyl-lysine (CML)-AGE content in food and investigated the association between dietary AGE intake and breast cancer (BrCa) risk. We assessed whether the risk was modified by race/ethnicity, obesity status, fruit and vegetable intake, BrCa invasiveness …

Exploring Breast Cancer Care Variation In Coc-Accredited Facilities, Sarah Grace Barron

Theses and Dissertations

INTRODUCTION: While improvements have been made in reducing breast cancer incidence and mortality over the past twenty years, disparities in breast cancer mortality remain. Understanding systematic differences in breast cancer treatment and quality of care remain at the epicenter of understanding breast cancer disparities. Needle biopsy is a less invasive and less expensive diagnostic test for breast cancer (as compared to excisional biopsy) and permits diagnosis while avoiding unnecessary surgery. This study was conducted to 1) examine how the National Quality Forum (NQF)-endorsed needle biopsy utilization measure varies geographically (i.e. state and region) and 2) determine the patient- and/or health …

Identifying Predictors Of Racial Disparity In Treatment And Mortality Among Patients Diagnosed With Breast Cancer In South Carolina, Oluwole Adeyemi Babatunde

Theses and Dissertations

Introduction: Despite a lower incidence of breast cancer (BrCA) among Black women in the U.S. compared to White women, Black women experience consistently higher mortality rates. The aims of this study were 1) to assess the relationship between race and diagnosis-to-treatment times 2) to assess racial disparity in mortality among Black and White BrCA patients in SC and 3) assessment of the validity of the Mortality-to- incidence ration (MIR) as a proxy for survival and geospatial investigation of racial disparity among breast cancer (BrCA) patients.

Methods: Breast cancer cases diagnosed between 2002-2010 were obtained retrospectively from the SC Central Cancer …

The Role Of Tumor And Tumor Microenvironment On Breast Cancer-Associated Adipocyte Plasticity, Janina V. Pearce

Theses and Dissertations

Cancer-associated cachexia is a condition defined by a sustained net-negative energy imbalance. Although the different types of adipose tissue – white, beige, and brown – have been implicated in contributing to cancer-associated cachexia, the mechanisms of these maladaptive changes and their impact on whole-body energy expenditure have not been fully elucidated. Using breast cancer as our model, we demonstrate white adipose tissue browning in murine and human breast cancer; furthermore, we demonstrate that this effect is extremely localized and takes place early in tumor progression. We utilized in vitro cell culture techniques and demonstrate that cancer secreted factors and cross-talk …

Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch

Theses and Dissertations

The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …

The Role Of Syndecan-1 And Extracellular Vesicles In Breast Cancer Brain Metastasis, Megan R. Sayyad

Theses and Dissertations

Breast cancer metastasizes to the brain in 15-30% of all breast cancer cases, and metastasis is the predominant cause of breast cancer-related deaths. Patients with HER2-enriched and triple-negative breast cancers (TNBCs) are more likely to develop brain metastases. While targeted therapies exist for HER2-enriched breast cancers, there are no effective treatments for TNBCs. Thus, a greater understanding of how these cancers spread to the brain is critical. In order to spread to the brain, disseminated breast cancer cells must overcome 2 major steps—crossing the blood-brain barrier (BBB) and survival and successful colonization of the distinctive and mostly cellular brain environment. …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Sarah Harmon Davis

Theses and Dissertations

Purpose: Knowledge of breast cancer genetics is critical for those at increased risk whomust make decisions about breast cancer screening options. The purpose of this study was toexplore cognitive and emotional variables that might influence knowledge of breast cancergenetics.Methods: This descriptive, exploratory study analyzed theory-based relationships amongvariables related to knowledge of breast cancer genetics in cancer families. Participants includedfirst-degree relatives of women with breast cancer who had received genetic counseling andtesting; participants themselves did not have breast cancer and had not received geneticcounseling or testing. Data were collected by telephone interview and survey. Variables analyzedinclude numeracy, health literacy, cancer-related distress, …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Sarah Harmon Davis

Theses and Dissertations

Purpose: Knowledge of breast cancer genetics is critical for those at increased risk whomust make decisions about breast cancer screening options. The purpose of this study was toexplore cognitive and emotional variables that might influence knowledge of breast cancergenetics.Methods: This descriptive, exploratory study analyzed theory-based relationships amongvariables related to knowledge of breast cancer genetics in cancer families. Participants includedfirst-degree relatives of women with breast cancer who had received genetic counseling andtesting; participants themselves did not have breast cancer and had not received geneticcounseling or testing. Data were collected by telephone interview and survey. Variables analyzedinclude numeracy, health literacy, cancer-related distress, …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Progesterone-Only Oral Contraceptive Pill, Breast Cancer, Heart Disease, And Stroke, Marsha Ema Samson

Theses and Dissertations

There is evidence from earlier studies that oral contraceptive pills may be a risk factor for certain chronic diseases, including heart disease, stroke, and breast cancer. Previous studies mainly focus on the estrogen component of combined (estrogen+ progestin) oral contraceptives (COCs) due to their popularity. This focus limits our understanding of progestin-only contraceptives and its relationship to commonly occurring chronic diseases. To provide insight into alternative methods of oral contraception, this dissertation explores the relationship between progestin-only oral contraceptive (POC) pills and heart disease, stroke, and breast cancer. We hypothesize that women using POCs are less likely to have certain …

Physical Activity And Breast Cancer In South Carolina, Chisom Onyeuku

Theses and Dissertations

This study examined the relationship between breast cancer incidence and recreational physical activity. It was one of the first studies in the southeastern US to examine incident breast cancer and physical activity in an ethnically diverse cohort of women. In terms of physical activity, both lifetime and recent physical activity were analyzed. All physical activity data were from validated self-reported surveys. The study examined BMI, menopausal status and race as key confounders and effect modifiers. The study found evidence that for Black women, there was a positive relationship between the amount of lifetime physical activity and the odds of incident …

Factors That Influence Breast Cancer Diagnoses In Virginia Women 40-64 Years Old Who Utlized The Every Woman’S Life Program 1998-2012, Melanie C. Dempsey

Theses and Dissertations

This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women.

The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source …

Improving Understanding Of Colorectal Cancer Screening Decisional Conflict And Breast Cancer Survivorship Care, Kara P. Wiseman

Theses and Dissertations

Background: Behavioral interventions and evidence based guidelines along the cancer control continuum can reduce the burden of cancer.

Objectives: This dissertation aims to increase our understanding of colorectal cancer screening (CRCS) decisional conflict and breast cancer survivorship care. This project: 1) assesses CRCS decisional conflict in a general population, 2) uses the Theory of Triadic Influence to model and evaluate direct and indirect associations between CRCS decisional conflict and colonoscopy adherence, 3) assesses post-treatment breast cancer care.

Methods: Data from a questionnaire administered to randomly selected adults, 50-75 years, living in six MN communities (N=1,268) and the 2010 Behavioral Risk …

Longitudinal Changes In The Inflammatory Potential Of Diet And Risk Of Cancer In Women, Fred Kinyuytabung

Theses and Dissertations

Introduction: The dietary inflammatory index (DII) assesses an individual’s overall diet quality with regards to its inflammatory potential on a continuum from maximally anti-inflammatory (lower or healthier DII scores) to maximally pro-inflammatory (higher or unhealthy DII scores). The DII measured at one point in time has been associated with cancer risk in previous studies; however, data are lacking regarding the change in DII over time and how these changes impact cancer risk. We assessed changes in the DII, and evaluated associations between cumulative history, and changes over time in dietary inflammatory potential, and risk of colorectal cancer (CRC) and breast …

Combined Antiproliferative Effects Of The Aminoalkylindole Win55,212-2 And Radiation In Breast Cancer Cells, Sean Emery

Theses and Dissertations

The potential antitumor activity of mixed CB1/CB2 cannabinoid receptor agonists, such as the aminoalkylindole WIN55,212-2 (WIN2), has been extensively studied, but little information is available as to their potential interaction with conventional cancer therapies, such as ionizing radiation (IR). In the present work, we investigated the effects of WIN2 on the antiproliferative effects of radiation in human (MCF-7 and MDA-MB-231) and murine (4T1) breast cancer cells, as well as an immortalized human breast epithelial cell line (MCF-10A). WIN2 or radiation alone inhibited breast tumor growth, while the combination of WIN2 and radiation was more effective than either agent alone in …

Treatment-Induced Breast Cancer Dormancy And Relapse, Rebecca Keim

Theses and Dissertations

When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor …

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

Effect Of Brassica Vegetable Intake On The 2:16Α Estrogen Metabolite Ratio In Postmenopausal European American And African American Women, Kendrea Knight

Theses and Dissertations

Background: It is well-established that many risk factors for breast cancer are related to estrogen or reproductive factors. Two estrogen metabolites of particular interest are 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16α-OHE) which are often reported together as a ratio of 2:16α-hydroxyestrone (2:16α –OHE). It has been demonstrated in several studies that postmenopausal women who are at a higher risk of breast cancer tend to have increased levels of 16α-OHE or decreased levels of 2-OHE levels in the body. Recent studies have shown that the phytochemical indole-3-carbinol (I3C), found in Brassica vegetables, impacts the conversion of 2-OHE, known as “good estrogen”, by …

Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl

Theses and Dissertations

Breast cancer is one of the most prevalent and deadly forms of cancer in women and is not restricted by race or ethnicity. Although a wealth of knowledge has been amassed on the biology of breast cancer, including its risk factors, diagnosis, prognosis, prevention, and treatment, it remains a serious health concern and active area of research. Initial response to standard chemotherapeutic and radiotherapeutic regimens is generally strong for many patients, yet breast tumors often recur, leading to more aggressive and resistant tumors. Because recurrence is such a clinical issue, more effective therapeutic approaches are needed to eliminate partial clinical …

Telomerase Inhibition And Sensitization Of Breast Tumor Cells, Kennon R. Poynter

Theses and Dissertations

Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anticancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditions chemo- and radio-therapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities.While various …

The Substituted Pyrrole Jb-03-14 Induces Autophagic Cell Death And Growth Arrest In Breast Tumor Cells, Christopher Ryan Arthur

Theses and Dissertations

The use of chemotherapy in the treatment of cancer has stimulated the demand for better chemotherapeutic agents that are more potent at destroying tumor cell populations and more selective for the specific tumor versus normal host tissues. This project is directed at discovering new anti-tumor agents that are effective against breast cancer based on structures derived from marine organisms, specifically brominated pyrroles. We utilized an in vitro breast cancer model to study the effects of pyrroles on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that the substituted pyrrole JG-03-14 induces time dependent …

Combinatorial Modulation Of Multiple Signaling Pathways To Gain Therapeutic Response In Breast And Prostate Cell Carcinomas, William Tressel Hawkins Ii

Theses and Dissertations

Our laboratory is primarily interested in novel pharmacological intervention of cell proliferation and survival pathways expressed in various types of cancer. These cyto-protective pathways can be activated in response to growth factor stimulation, toxic insult and radiation. In our studies, we utilized novel drug combinations with and without radiation to enhance breast & prostate tumor cell death both in vitro and in vivo. Previous studies from our group have shown that UCN-01 and MEK1/2 inhibitors interact to cause tumor cell death in transformed cell lines in vitro. We extended this observation to an in vivo animal model system using the …

Influence Of The Vitamin D3 Analog Eb 1089 On Senescence And Cell Death Pathways In The Response Of Breast Tumor Cells To Ionizing Radiation, Gerald Alan Demasters

Theses and Dissertations

A senescence-like growth arrest succeeded by rapid recovery of proliferative capacity is observed in MCF-7 breast tumor cells exposed to fractionated radiation (5 x 2Gy) alone. Exposure to the vitamin D3 analog EB 1089 (100nM) prior to irradiation converts the initial growth arrest response to cell death in part through the inhibition of radiation-induced senescence and promotion of both apoptotic and autophagic cell death. More importantly, EB 1089 was shown to profoundly reduce the rate of recovery following fractionated irradiation. The effect of EB 1089 on the temporal response to radiation is also observed in MCF-7 cells expressing caspase 3, …