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.

Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis

“…Furthermore, the racial disparity in breast cancer patients is predominantly present in TNBC and three times higher in AA women with TNBC in comparison to other ethnicities [14]. Together, this unique phenomenon may explain the association of high exo-AnxA2 with the aggressiveness of TNBC observed in AA women [14][15][16][17]30].…”

“…Overall, TNBC is associated with poor prognosis, high mortality rate, shorter median time to relapse (due to its aggressive tumor phenotypes), high recurrence rate, and visceral metastatic spread to the brain and lungs. The disparities in breast cancer seen in African-American (AA) women may arise due to biological factors such as obesity, tissue inflammation and altered phosphoprotein signaling, and environmental causes such as unsafe neighborhoods, access to healthcare treatment, low family income, stress, and exposure to environmental carcinogens [14][15][16][17]. Though life style and genetic differences are correlated with high incidence of basal breast carcinomas in AA women after adjusting for socioeconomic factors, the incidence and mortality rate remains higher than other ethnicities.…”

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

“…This health disparity may arise due to diagnosis at later stages of the disease (35) or a predisposed racially distinct genetic or epigenetic profile (36,37) with a propensity toward an overactive oncogenic p38 MAPK, Wnt/β-catenin, IGF2/ERbeta signaling axis (38)(39)(40). Additional factors to a health disparity arising in AA women regarding TNBC include vitamin D deficiencies (41) socioeconomic factors, later stage diagnosis, obesity, or even breast feeding patterns (42)(43)(44).…”

Quest for Tangible Biomarkers for Triple-Negative Breast Cancer

“…In addition, the M and MSL subtypes have been shown to be responsive to dasatinib (SRC inhibitor), NVP-BEZ235 (PI3K/mTOR inhibitor), and c-MET and VEGFR2-targeting regimens as predicted by their distinctive molecular makeup. Supported by in vitro and in vivo analyses, active clinical evaluation of the anti-VEGF mAb, bevacizumab, is currently underway for metastatic TNBC (7). Characterized by the expression of androgen receptor (AR), the LAR TNBC subtype exhibits sensitivity to AR antagonism (bicalutamide and enzalutamide; ref.…”

“…Although different mutational landscapes within TNBCs could converge on a few kinases, there is variability among kinase activation and distribution patterns, suggesting that unique combinations of kinase-targeting drugs might prove effective, whereas single agents may not. It is interesting to note that several MEK (a component of the MAPK/ERK pathway) inhibitors including cobimetinib, selumetinib, and trametinib are being investigated in patients with TNBC (7) along with other kinase inhibitors.…”