Racial Disparities in Triple Negative Breast Cancer: A Review of the Role of Biologic and Non-biologic Factors

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). TNBC constitutes about 15–30 percent of all diagnosed invasive breast cancer cases in the United States. African-American (AA) women have high prevalence of TNBC with worse clinical outcomes than European-American (EA) women. The contributing factors underlying racial disparities have been divided into two major categories based on whether they are related to lifestyle (non-biologic) or unrelated to lifestyle (biologic). Our objective in the present review article was to understand the potential interactions by which these risk factors intersect to drive the initiation and development of the disparities resulting in the aggressive TNBC subtypes in AA women more likely than in EA women. To reach our goal, we conducted literature searches using MEDLINE/PubMed to identify relevant articles published from 2005 to 2019 addressing breast cancer disparities primarily among AA and EA women in the United States. We found that disparities in TNBC may be attributed to racial differences in biological factors, such as tumor heterogeneity, population genetics, somatic genomic mutations, and increased expression of genes in AA breast tumors which have direct link to breast cancer. In addition, a large number of non-biologic factors, including socioeconomic deprivation adversities associated with poverty, social stress, unsafe neighborhoods, lack of healthcare access and pattern of reproductive factors, can promote comorbid diseases such as obesity and diabetes which may adversely contribute to the aggression of TNBC biology in AA women. Further, the biological risk factors directly linked to TNBC in AA women may potentially interact with non-biologic factors to promote a higher prevalence of TNBC, more aggressive biology, and poor survival. The relative contributions of the biologic and non-biologic factors and their potential interactions is essential to our understanding of disproportionately high burden and poor survival rates of AA women with TNBC.

Patient-derived triple negative breast cancer organoids provide robust model systems that recapitulate tumor intrinsic characteristics

“…Samples were collected from patients of various age groups (Fig 1C ) and diverse ethnic and racial backgrounds (Fig 1D). An increased proportion of TNBC tumor samples was observed from black patients with African or west-Indian heritage (Fig 1D,Table S1) which recapitulates the higher incidence of TNBCs in the African-American community (Perou, 2011;Prakash et al, 2020). Using a DNA-seq panel of 143 cancer driver genes, we identified pathogenic single nucleotide variants (SNVs) in 45 tumor organoid lines (Fig 1E ); PIK3CA was mutated in 33% of the tumor organoids, the majority of which were from patients with luminal breast cancer.…”

Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients

“…The relationship between BRCA1 mRNA levels and frequency of African American patients was statistically significant based on a Fisher’s exact test of the contingency table shown in Supplementary Table 1. As African American women are more likely to get BC (particularly TNBC) [ 26 ], this result is surprising because we found that low expression of BRCA1 mRNA correlated with better outcomes in BC ( Figure 1 ).…”

Genomics and Cancer Disparities: The Justice and Power of Inclusion

“…For example, the gene signatures that define breast cancer subtypes have shaped our approaches to developing research for targeted therapies; however, we also find that gene signatures have significant variation across patient groups, underlying a bias in the incidence of specific subtypes within these patient groups. Specifically, we now know that triple-negative breast cancers (TNBC) are more prevalent in non-White populations (12) and that the subtypes of TNBC, defined by the genomic signature of hundreds of genes, also show significant bias among race groups (13). Yet, knowing this does not necessarily change the course of treatment.…”