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.

Racial health disparities in ovarian cancer: not just black and white

“…Interestingly, PSPHL levels are relatively higher in AA breast tumors than the CA breast tumors [ 33 ]. Health disparities in breast cancer are well documented [ 34 , 35 ] and the study on PSPHL in breast tumors [ 33 ] identified partial deletion (30Kb long fragment) of chromosome 7p11 in CA women, which led to attenuation of expression of PSPHL in CA breast tumors. No such mechanism was proposed for observed disparate expression of PSPHL in OCs of AA vs. CA origin, and would be interesting to elucidate.…”

Autotaxin and Breast Cancer: Towards Overcoming Treatment Barriers and Sequelae

“…Breast cancer has become the prototypical model for the tumor microenvironment, in part because its interactions with tumor stroma and adjacent breast tissue are complex and our understanding of these events is at an elementary stage [23]. Deconvoluting these interactions and developing selective pharmacological approaches to break the communications between cancer cells and stroma could have as great an impact on cancer therapy in the next ten years as immunotherapy has had over the last decade.…”

Pan‐cancer clinical and molecular analysis of racial disparities

“…45 For instance, differential expression of inflammatory mediators, such as IL-6, and inflammatory cytokines have been found to be disproportionally increased in AA patients with breast cancer. This greater risk of death was consistent across 2 large databases of patients with cancer and persisted despite controlling for socioeconomic factors, access to care, and insurance status.…”

“…This knowledge adds to a growing body of evidence that racial disparities may be caused by genetic and biological differences. 45 For instance, differential expression of inflammatory mediators, such as IL-6, and inflammatory cytokines have been found to be disproportionally increased in AA patients with breast cancer. 46 In addition, both mediators of angiogenesis (vascular endothelial growth factor),and immune cells with a tumor-promoting phenotype (tumor-associated macrophages) have been found to be increased in tumors from AA patients.…”