Racial Disparity in Quadruple Negative Breast Cancer: Aggressive Biology and Potential Therapeutic Targeting and Prevention

Jinna, Nikita; Jovanovic-Talisman, Tijana; LaBarge, Mark A.; Natarajan, Rama; Kittles, Rick A.; Sistrunk, Christopher; Rida, Padmashree C.G.; Seewaldt, Victoria L.

doi:10.3390/cancers14184484

Cited by 8 publications

(5 citation statements)

References 118 publications

(168 reference statements)

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“…MiRNA profiling of the TNBC tumor cells (and of several other types of tumors) can vary according to the populational group studied [20,26,[39][40][41][42][43][44]. Most of the data are, however, in the comparison of NHW to AA TNBC patients [26,40,[44][45][46][47]. In our previous study, we reported that ancestrally characterized AA patients, when compared to NHW, exhibited distinct patterns of copy number alterations (CNAs) and miRNA expression profiles in both their TNBC and non-TNBC tumor tissues [44].…”

Section: Introductionmentioning

confidence: 99%

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Almohaywi,

Sugita,

Centa

et al. 2023

IJMS

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Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.

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Section: Introductionmentioning

confidence: 99%

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Almohaywi,

Sugita,

Centa

et al. 2023

IJMS

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“…Prior studies 25 have reported that African American females have higher rates in general of QNBC, a TNBC subtype characterized by the lack of AR expression. Our data suggest that the higher incidence of QNBC may be specific to younger African American patients, demonstrated by the significant downregulation of AR in TNBC tumors of this population compared with older African American patients.…”

Section: Discussionmentioning

confidence: 98%

Epigenetic Profiles of Triple-Negative Breast Cancers of African American and White Females

Ensenyat-Mendez,

Solivellas-Pieras,

Llinàs-Arias

et al. 2023

JAMA Netw Open

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ImportanceTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and appears to have disproportionately higher incidence and worse outcomes among younger African American females.ObjectiveTo investigate whether epigenetic differences exist in TNBCs of younger African American females that may explain clinical disparities seen in this patient group.Design, Setting, and ParticipantsThis cross-sectional study used clinical, demographic, DNA methylation (HumanMethylation450; Illumina), and gene expression (RNA sequencing) data for US patient populations from publicly available data repositories (The Cancer Genome Atlas [TCGA], 2006-2012, and Gene Expression Omnibus [GEO], 2004-2013) accessed on April 13, 2021. White and African American females with TNBC identified in TCGA (69 patients) and a validation cohort of 210 African American patients from GEO (GSE142102) were included. Patients without available race or age data were excluded. Data were analyzed from September 2022 through April 2023.Main Outcomes and MeasuresDNA methylation and gene expression profiles of TNBC tumors by race (self-reported) and age were assessed. Age was considered a dichotomous variable using age 50 years as the cutoff (younger [&lt;50 years] vs older [≥50 years]).ResultsA total of 69 female patients (34 African American [49.3%] and 35 White [50.7%]; mean [SD; range] age, 55.7 [11.6; 29-82] years) with TNBC were included in the DNA methylation analysis; these patients and 210 patients in the validation cohort were included in the gene expression analysis (279 patients). There were 1115 differentially methylated sites among younger African American females. The DNA methylation landscape on TNBC tumors in this population had increased odds of enrichment of hormone (odds ratio [OR], 1.82; 95% CI, 1.21 to 2.67; P = .003), muscle (OR, 1.85; 95% CI, 1.44 to 2.36; P &lt; .001), and proliferation (OR, 3.14; 95% CI, 2.71 to 3.64; P &lt; .001) pathways vs other groups (older African American females and all White females). Alterations in regulators of these molecular features in TNBCs of younger African American females were identified involving hormone modulation (downregulation of androgen receptor: fold change [FC] = −2.93; 95% CI, −4.76 to −2.11; P &lt; .001) and upregulation of estrogen-related receptor α (FC = 0.86; 95% CI, 0.34 to 1.38; P = .002), muscle metabolism (upregulation of FOXC1: FC = 1.33; 95% CI, 0.62 to 2.03; P &lt; .001), and proliferation mediators (upregulation of NOTCH1: FC = 0.71; 95% CI, 0.23 to 1.19; P = .004 and MYC (FC = 0.81; 95% CI, 0.18 to 1.45; P = .01).Conclusions and RelevanceThese findings suggest that TNBC of younger African American females may represent a distinct epigenetic entity and offer novel insight into molecular alterations associated with TNBCs of this population. Understanding these epigenetic differences may lead to the development of more effective therapies for younger African American females, who have the highest incidence and worst outcomes from TNBC of any patient group.

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“…African American (AA) women have significantly higher mortality rates from breast cancer (BC) than White (W) women with the same disease and patient variables despite having a lower incidence of disease [ 1 , 2 , 3 , 4 , 5 , 6 ]. Genetic [ 7 ] and epigenetic [ 8 ] differences in cancer cells [ 9 ] and genetic, immune, and inflammatory differences and vitamin D deficiency in the tumor microenvironment [ 8 , 10 , 11 ] contribute to more aggressive cancer characteristics and, in combination with extensive and well-documented socioeconomic factors [ 12 , 13 ], collectively generate a worse prognosis.…”

Section: Introductionmentioning

confidence: 99%

Temporal Association Rule Mining: Race-Based Patterns of Treatment-Adverse Events in Breast Cancer Patients Using SEER–Medicare Dataset

Adam,

Wieder

2024

Biomedicines

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PURPOSE: Disparities in the screening, treatment, and survival of African American (AA) patients with breast cancer extend to adverse events experienced with systemic therapy. However, data are limited and difficult to obtain. We addressed this challenge by applying temporal association rule (TAR) mining using the SEER–Medicare dataset for differences in the association of specific adverse events (AEs) and treatments (TRs) for breast cancer between AA and White women. We considered two categories of cancer care providers and settings: practitioners providing care in the outpatient units of hospitals and institutions and private practitioners providing care in their offices. PATIENTS AN METHODS: We considered women enrolled in the Medicare fee-for-service option at age 65 who qualified by age and not disability, who were diagnosed with breast cancer with attributed patient factors of age and race, marital status, comorbidities, prior malignancies, prior therapy, disease factors of stage, grade, and ER/PR and Her2 status and laterality. We included 141 HCPCS drug J codes for chemotherapy, biotherapy, and hormone therapy drugs, which we consolidated into 46 mechanistic categories and generated AE data. We consolidated AEs from ICD9 codes into 18 categories associated with breast cancer therapy. We applied TAR mining to determine associations between the 46 TR and 18 AE categories in the context of the patient categories outlined. We applied the spark.mllib implementation of the FPGrowth algorithm, a parallel version called PFP. We considered differences of at least one unit of lift as significant between groups. The model’s results demonstrated a high overlap between the model’s identified TR-AEs associated set and the actual set. RESULTS: Our results demonstrate that specific TR/AE associations are highly dependent on race, stage, and venue of care administration. CONCLUSIONS: Our data demonstrate the usefulness of this approach in identifying differences in the associations between TRs and AEs in different populations and serve as a reference for predicting the likelihood of AEs in different patient populations treated for breast cancer. Our novel approach using unsupervised learning enables the discovery of association rules while paying special attention to temporal information, resulting in greater predictive and descriptive power as a patient’s health and life status change over time.

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Racial Disparity in Quadruple Negative Breast Cancer: Aggressive Biology and Potential Therapeutic Targeting and Prevention

Cited by 8 publications

References 118 publications

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Epigenetic Profiles of Triple-Negative Breast Cancers of African American and White Females

Temporal Association Rule Mining: Race-Based Patterns of Treatment-Adverse Events in Breast Cancer Patients Using SEER–Medicare Dataset

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