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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37796506", "kind": "science-record", "revision": 4, "content_hash": "sha256:3a637e925e395e6a70275f6d0c6a111b0eff2a3dbd11f164e49f14c3e31c8dc5", "created_at": "2026-11-01T19:02:39Z", "updated_at": "2026-11-01T22:10:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Epigenetic Profiles of Triple-Negative Breast Cancers of African American and White Females.", "doi": "10.1001/jamanetworkopen.2023.35821", "pmid": "37796506", "authors": ["Miquel Ensenyat-Mendez", "Maria Solivellas-Pieras", "Pere Llinàs-Arias", "Sandra Íñiguez-Muñoz", "Jennifer L Baker", "Diego M Marzese", "Maggie L DiNome"], "journal": "JAMA network open", "year": 2023, "abstract": "Importance: Triple-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.\nObjective: To investigate whether epigenetic differences exist in TNBCs of younger African American females that may explain clinical disparities seen in this patient group.\nDesign, Setting, and Participants: This 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.\nMain Outcomes and Measures: DNA 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 [<50 years] vs older [≥50 years]).\nResults: A 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 < .001), and proliferation (OR, 3.14; 95% CI, 2.71 to 3.64; P < .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 < .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 < .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).\nConclusions and Relevance: These 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.", "claims": [{"id": "claim-method", "statement": "Differentially methylated sites (DMSs) were computed using the Wilcoxon test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37796506", "locator": "sections[4] \"Statistical Analysis\" paragraph 3", "quote": "Differentially methylated sites (DMSs) were computed using the Wilcoxon test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This 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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37796506", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "This 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."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In a cross-sectional study of 69 female patients with TNBC, tumors of younger African American patients had a distinct DNA methylation profile compared with those of older African American females and White females of all ages.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37796506", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In this cross-sectional study of 69 female patients with TNBC, tumors of younger African American patients had a distinct DNA methylation profile compared with those of older African American females and White females of all ages."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In a cross-sectional study of 69 female patients with TNBC, tumors of younger African American patients had a distinct DNA methylation profile compared with those of older African American females and White females of all ages.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37796506"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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