Racial Disparity and Triple-Negative Breast Cancer in African-American Women: A Multifaceted Affair between Obesity, Biology, and Socioeconomic Determinants

Abstract

Triple negative breast cancer (TNBC) is a molecularly heterogeneous disease whose incidence is disproportionately higher in African American (AA) women compared to European American (EA) women. Earlier onset, more advanced stage at diagnosis, and aggressive tumor phenotype are some of the characteristic features of TNBC in women with African ethnicity in comparison to EA women, denoting one of the most significant examples of racial disparity in oncology. It is still contentious whether health disparities result in aggressive behavior of TNBC in AA women or it is indeed a molecularly distinct disease. Given the "gaps-in-knowledge" surrounding racial disparity in TNBC, this review discusses various socioeconomic factors and the genetic predispositions contributing to poor prognosis of TNBC in AA women. While socioeconomic factors may contribute to poorer survival, multiple preclinical and clinical studies suggest inherent genetic risk factors and aberrant activation of oncogenic pathways in AA TNBC. Additionally, AA women are more likely to be obese and obesity is known to drive a molecular circuitry resulting in aggressive tumor progression indicating a potential obesity-TNBC axis at work in AA women. Given the multifactorial nature of AA TNBC, a transdisciplinary approach may help bridge the disparity that exists between AA and EA TNBC.

Keywords: African-American; obesity; racial disparity; risk factors; triple negative breast cancer.

Figure 1

Schematic illustrating the molecular subtypes of breast cancer. The blue circle groups six different subtypes of triple-negative breast cancer (TNBC) and demonstrate the characteristics of these subtypes. Subtypes of TNBC: BL1, basal-like 1; BL2, basal-like 2; IM, immunomodulatory; ML, mesenchymal-like; MSL, mesenchymal stem-like; LAR, luminal androgen receptor.

Figure 2

Overview of various socioeconomic and biological factors contributing to disparity in TNBC progression in African American (AA) versus European American (EA) women. Various socioeconomic factors such as low income and poor access to health care can aid in high prevalence of obesity. Obese state can modify various signaling pathways and directly impact various tumor-promoting biological process including growth, invasion, and migration. These socioeconomic and biological factors contribute to TNBC progression in AA women directly or indirectly.

Figure 3

Prevalence of triple negative breast cancer (TNBC) is shown among European American (EA), African American (AA) and women with African ancestry.

Figure 4

Adipocytes in obese state secrete proinflammatory cytokines in the tumor microenvironment and induce the major hallmarks of cancer development (proliferation, survival, migration, invasion, and angiognesis).

Figure 5

Biological and non-biological factors that contribute to TNBC disparity. Biological factors include obesity, cancer stem cell signaling pathways, markers, and genetic causes. Socioeconomic factors are major non-biological factors that play an important role in TNBC disparity.