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.
Highlights
Breast cancer is the second-most common cancer and a leading cause of cancer-related mortality for women in United States [1]
Breast cancer has been historically sub-classified on the basis of three molecular markers; estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (EGFR2/Her2), whose presence/absence guide the prognosis and therapeutic interventions
triple-negative breast cancer (TNBC) are associated with worse prognosis, early relapse after standard chemotherapy, a high frequency of metastasis to lung, liver and brain and relapse after standard chemotherapy, a high frequency of metastasis to lung, liver and brain and a a low overall survival compared to other breast cancer subtypes
Summary
Breast cancer is the second-most common cancer and a leading cause of cancer-related mortality for women in United States [1]. DNA microarrays [4,5] into six different subtypes, namely, luminal A (ER+ and/or PR+ and HER2−), luminal B (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER−, PR− and HER2+), normal-like, claudin-low and basal-like/TNBC (ER/PR/HER2 negative, cytokeratin 5/6+ and/or epidermal growth factor receptor+) (Figure 1) [3,5,6]. This classification varies in prognosis and therapeutic. High cost of molecular analysis along with limited availability expertise and the infrastructure of the limitations have preventedthat the have introduction of this of bioinformatics expertise and are the some infrastructure are somethat of the limitations prevented the classification of system as standard practice into clinics. practice into clinics
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