All ETDs from UAB

Advisory Committee Chair

Theresa V Strong

Advisory Committee Members

Mona N Fouad

Andra R Frost

Bruce R Korf

Susan M Sell

Document Type

Dissertation

Date of Award

2009

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Breast cancer is the second leading cause of cancer related death among women in the United States, surpassed only by lung cancer. It is estimated that over 200,000 women developed breast cancer and more than 40,000 died of the disease in 2008 alone. Although the overall incidence of breast cancer is lower in African-American women, the incidence of early-onset breast cancer is higher than that observed in European-American women. African-American women also have higher mortality rates due to this disease than those observed in their European-American counterparts. Breast cancer exhibits heterogeneity at the molecular, cellular, and clinical levels, and the underlying cause of the comparatively aggressive nature of breast cancer in African-American women is not well understood. The application of advanced techniques in molecular biology is needed to characterize differences in breast tumor biology as they relate to breast cancer health disparities between African-American and European-American women. In this dissertation, the role of biology and genome copy number changes is examined in relation to ethnicity and breast cancer subtypes. African-American breast tumors are described as biologically distinctive from European-American breast tumors. Also, the molecular basis for this distinction is linked to the development of more iv aggressive breast cancer subtypes in African-American women. Differences in the biological character of breast cancer subtypes were associated with specific genome copy number alteration events. Overall, the copy number alteration profiles were similar between the two ethnic groups when controlling for tumor subtype and histological grade; however, several alterations distinguished breast tumors by ethnicity. Finally, evidence is presented suggesting that these genome copy number events underlie the differences in breast cancer presentation observed between African-American and European-American women due to an increased propensity of African-American women to develop aggressive basal breast cancer subtype.

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