Abstract
BackgroundAfrican-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity.Methods and ResultsUsing laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors.ConclusionsThe gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers. Notably, pathways related to tumor angiogenesis and chemotaxis could be functionally different in these two patient groups.
Highlights
The age-adjusted breast cancer incidence and mortality rates vary substantially among race/ethnic groups [1]
The gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers
Characteristics of study population Total RNA was isolated from laser capture microdissection (LCM)-dissected tumor epithelia and tumor stroma of 35 breast tumors (18 African-American and 17 European-American breast cancer patients)
Summary
The age-adjusted breast cancer incidence and mortality rates vary substantially among race/ethnic groups [1]. European-American women have the highest risk of developing the disease, while African-American women experience the highest mortality rates This difference in survival between African-American and European-American breast cancer patients has been attributed to differences in socioeconomic factors and access to healthcare. It has been proposed that differences in tumor biology may contribute to the survival health disparity associated with breast cancer [6,7]. Because the basal-like subtype is a poor prognosis marker, its increased frequency among AfricanAmerican patients, when compared with non-African-American patients, could contribute to their disproportionately high breast cancer mortality. African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity
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