Emerging evidence for the role of differential tumor microenvironment in breast cancer racial disparity: a closer look at the surroundings

Abstract

Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences. Tumor microenvironment, which provides a favorable niche for the growth of tumor cells, is comprised of several types of stromal cells and the various proteins secreted as a consequence of bi-directional tumor-stromal cross-talk. Emerging evidence suggests inherent biological differences in the tumor microenvironment of breast cancer patients from different racial backgrounds. Tumor microenvironment components, affected by the genetic make-up of the tumor cells as well as other non-tumor-associated factors, may also render patients more susceptible to the development of aggressive tumors and faster progression of disease resulting in early onset, thus adversely affecting patients' survival. This review provides an overview of breast cancer racial disparity and discusses the existence of race-associated differential tumor microenvironment and its underlying genetic and non-genetic causal factors. A better understanding of these aspects would help further research on effective cancer management and improved approaches for reducing the racial disparities gaps in breast cancer patients.

Figure 1.

Racially-disparate tumor microenvironment in breast tumors. The TME of BC contains tumor cells, macrophages, dendritic cells, adipocytes, fibroblasts, cytokines and growth factors. Higher vessel density, increased macrophage recruitment and elevated cytokines create differential TME in BC patients of AA racial group. The inflammatory microenvironment induced growth, angiogenesis, metastasis and therapy resistance ultimately leads to poor clinical outcome in AA BC patients.

Figure 2.

Factors associated with breast cancer racial disparities. TME is a result of complex interplay of multiple factors such as socioeconomic, life style and obesity. Socioeconomics and lifestyle may give rise to the incidence of obesity further contributing to differential TME in AA population. Altered TME fuels BC progression and significantly contributes to early onset, aggressive tumor phenotype and poor survival leading to BC racial disparity.