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Updated: Mar 15, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Genetic Ancestry using Mitochondrial DNA in patients with Triple-negative breast cancer (GAMiT study)
Roshni Rao1, Aeisha Rivers1, Asal Rahimi2
1Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
Background:
Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2)/neu receptors, and is aggressive and therapeutically challenging. Genetic ancestry testing is an emerging medical field. Mitochondrial DNA (mtDNA), which is distinct from nuclear DNA, is maternally inherited and allows for origin determination. Patients with TNBC tend to be younger and are more likely to be African American, making this an ideal disease for mtDNA exploration. To the authors' knowledge, the current study is the first to perform mtDNA for self-described African American, White, and Hispanic patients with TNBC to identify mtDNA patterns.
Methods:
Patients with TNBC who were at any stage of therapy/survivorship were included. Self-reported ethnicity was confirmed at the time of the prospective buccal swab. Haplogroup prediction was performed on sequencing of hypervariable region 1. Using sequence similarity scores and lineage databases, sequence patterns were determined. Data regarding presentation and treatment, tumor features, and outcomes was collected.
Results:
A total of 92 patients were included: 31 self-described African American, 31 White, and 30 Hispanic individuals. Hispanic patients were found to have the largest tumor size (4.5 cm; P = .01) and youngest age (41 years; P<.0001). Eight patients were BRCA1/2 mutation carriers. There were no differences noted among groups with regard to surgery, lymph node metastases, or survival. Analysis revealed Nigerian, Cameroon, or Sierra Leone ancestry and haplogroups A, U, H, or B to be the most common mtDNA patterns. Twelve discordances (13%) between mtDNA analysis and self-described ethnicity were identified among the 92 patients. The highest discordance (26%; 8 patients) was noted in self-described Hispanic patients: 3 had Nigerian ancestry, and 1 individual demonstrated haplogroup K mtDNA (Ashkenazi Jewish ancestry).
Conclusions:
Discordance between self-reported ethnicity and mtDNA analysis was identified in 13% of patients with TNBC. The identification of mtDNA patterns with a predisposition toward TNBC may allow for risk stratification. Cancer 2017;107-113. © 2016 American Cancer Society.
Insights
Mitochondrial DNA (mtDNA) analysis revealed ancestry patterns in triple-negative breast cancer (TNBC) patients, with 13% showing discordance between mtDNA and self-reported ethnicity. This finding may aid in TNBC risk stratification.
Area of Science:
- Genetics
- Oncology
- Anthropology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking standard therapeutic targets.
- Mitochondrial DNA (mtDNA) analysis offers insights into maternal lineage and population origins.
- TNBC disproportionately affects younger, African American populations, making mtDNA exploration relevant.
Purpose of the Study:
- To investigate mitochondrial DNA (mtDNA) patterns in patients with triple-negative breast cancer (TNBC).
- To identify potential correlations between mtDNA haplogroups, self-reported ethnicity, and TNBC characteristics.
- To explore the utility of mtDNA analysis for risk stratification in TNBC.
Main Methods:
- Prospective collection of buccal swabs from TNBC patients for DNA sequencing.
- Analysis of the hypervariable region 1 of mtDNA for haplogroup prediction.
- Comparison of mtDNA-derived ancestry with self-reported ethnicity and clinical data.
Main Results:
- A total of 92 TNBC patients (31 African American, 31 White, 30 Hispanic) were analyzed.
- Hispanic patients presented with larger tumor size and younger age at diagnosis.
- A 13% discordance rate was observed between mtDNA ancestry and self-reported ethnicity, notably higher in Hispanic patients.
Conclusions:
- Mitochondrial DNA (mtDNA) analysis revealed distinct ancestral patterns in TNBC patients.
- Significant discordance between self-reported ethnicity and genetic ancestry was identified.
- mtDNA profiling may offer a novel approach for risk stratification in triple-negative breast cancer.
