Disparities in breast cancer outcomes between Caucasian and African American women: a model for describing the relationship of biological and nonbiological factors

Abstract

Breast cancer is the most common malignancy in women in the United States but significant disparities exist for African American women compared to Caucasian women. African American women present with breast cancer at a younger age and with a greater incidence under the age of 50 years, develop histologically more aggressive tumors that are at a more advanced stage at presentation, and have a worse disease-free and overall survival than Caucasian women. The biological characteristics of the primary tumor play an important role in determining the outcome of the disparity, and significant differences have been identified between African American and Caucasian breast cancer in steroid receptor and growth factor receptor content, mutations in cell cycle components, chromosomal abnormalities, and tumor suppressor and other cancer genes. The consequences of the biological factors are influenced by a variety of nonbiological factors, including socioeconomic, health care access, reproductive, and confounding factors. The nonbiological factors may act directly to enhance (or inhibit) the consequences of the biological changes, indirectly to facilitate outcome of the disparity, or as a cofounding factor, driving the association between the biological factors and the disparity. The prevention and management of the disparities will require an understanding of the relationship of biological and nonbiological factors. The present review was undertaken to promote this understanding by describing the biological basis of the four major disparities - early age of onset, more advanced stage of disease, more aggressive histologic changes, and worse survival - and the important relationship to the nonbiological factors. A model is proposed to provide a comprehensive view of this relationship, with the goal of facilitating an understanding of each disparity and the issues that need to be addressed to eliminate the disparity.

Figure 1

A model for the initiation and development of breast cancer disparities in African American versus Caucasian women. The model depicts the relationship of biological abnormalities that occur to a greater extent in the tumors of African American women, and nonbiological factors that are more frequent in African Americans, in the initiation and development of breast cancer disparities. The biological activities are considered to be the main contributing factors to the type and outcome of the disparities. The nonbiological activities are considered to influence primarily the biological activities, and are organized according to what is considered to be the main manner of influence on the biological activities - to promote or inhibit, to facilitate, or to act as confounding factors. It is through this influence on biological activities that the nonbiological factors influence disparity outcome. The nonbiological factors may also influence the disparity directly, although this is considered to be less common. The nonbiological factors are depicted in overlapping circles to indicate that they may interact with each other, and the nonbiological factors may act alone or in combination to influence these outcomes. ER, estrogen receptor.

Figure 2

Cell cycle phases and the regulatory components important in breast cancer disparities. Abnormalities (highlighted in red) have been identified in multiple regulatory components of the cell cycle in the breast cancer of African American compared with Caucasian women. These include cyclins A, B, D, and E, p16/INK4A, the tumor suppressor genes p53 and RASSF1A, as well as endogenous hormones and growth factors. Retinoblastoma protein (pRb) has not been studied in African American breast cancer, but evidence suggests this may be altered as well.