Date of Award

12-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Healthcare Genetics

Committee Member

Dr. Julie Eggert, Committee Chair

Committee Member

Dr. Stephen Dyar

Committee Member

Dr. Jim McDonell

Committee Member

Dr. Paula Watt

Abstract

The first chapter of this dissertation serves as an overview of the background and significance of this study, the associations between hereditary breast cancer susceptibility gene alterations (GA) and aggressive tumor phenotypes in women with breast cancer. The body of work in all chapters focuses on the topics of breast cancer genomics, inflammatory breast cancer, the application of Protection Motivation Theory to guide prevention strategies for women with breast cancer diagnosis and positive genetic alteration, and the associations between hereditary breast cancer susceptibility GAs and aggressive tumor phenotype. The second chapter is a review of literature to discuss breast cancer genomics, specifically two genes, Ataxia Telangiectasia Mutated (ATM) and the Partner and Localizer of BRCA2 (PALB2). The results of the review highlight the importance of identifying two new breast cancer susceptibility genes, other than the well known BRCA1and BRCA2, and the requirement of including these genes in standard breast cancer genetic testing. The third chapter is a review of literature to describe inflammatory breast cancer (IBC), pathogenicity of the disease and genomic investigation of IBC. IBC is an aggressive type of breast cancer with poor prognosis responsible for 2.5% of all new breast cancers. The majority of IBC patients are diagnosed with triple negative breast cancer (TNBC), which is the aggressive phenotype. The fourth chapter provides an overview of literature that describes the Protection Motivation Theory (PMT) and how it has been applied in a variety of research settings. A pilot study is suggested including PMT and its application for breast cancer prevention strategies uptake by patients who have a diagnosis of breast cancer. The pilot study would use a focus group of women with breast cancer to determine if the theory can guide prevention strategies for women with a mutation that causes the high risk to develop multiple types of primary cancers over their lifetime. The fifth chapter describes the dissertation work; a quantitative study that analyzes associations between aggressive breast cancer phenotypes in a population of women at high risk for hereditary breast cancer and specific GAs. The final chapter, is a synthesis of all manuscripts related to the breast cancer in the high risk population of women to develop this dreaded disease; breast cancer genomic investigation of ATM and PALB2 genes, the aggressive IBC, PMT application for breast cancer prevention strategies uptake and association of GAs and aggressive breast cancer phenotype. The populations in all the articles were women diagnosed with breast cancer and were at high risk of hereditary breast cancer syndromes. As a result of these manuscripts, it is expected to make suggestions for genetic testing guidelines to include multi-panel genetic testing for all eligible individuals as well as inclusion of tumor biomarkers and ethnicity in eligibility criteria. It is also recommended to apply PMT to encourage adherence to prevention strategies in order to reduce the risk of additional cancer primary.

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