Molecular Subtyping of Triple-negative Breast Cancer and African Ancestry-related Immunogenicity
- Conditions
- Triple Negative Breast Cancer
- Interventions
- Genetic: DNA and whole transcriptome mRNA sequencing
- Registration Number
- NCT05111067
- Lead Sponsor
- Nova Scotia Health Authority
- Brief Summary
Triple-negative breast cancer (TNBC) is a heterogeneous disease that is associated with a younger age of onset, worse stage matched-outcomes, and women of African ancestry in North America. A higher incidence of TNBC is also seen in West Africa, despite unique environmental, socioeconomic and modifiable risk factors. Transcriptome analysis of TNBC has delineated four distinct subgroups with therapeutic and prognostic significance. With further characterization, important regional differences have emerged between populations of African vs. European ancestry. These differences may have significant implications for the efficacy of novel TNBC-targeted therapy and need to be further evaluated. Transcriptional data on TNBC in sub-Saharan African also offers the opportunity to evaluate the relationship between breast cancer phenotype and ancestry-linked differences in the tumor-immune microenvironment.
- Detailed Description
This study seeks to characterize the mRNA profile of TNBC in Nigeria and compare to a reference population in Nova Scotia. Insight into the unique tumor-immune profile of TNBC in Nigeria and the link between the West African-linked Duffy-antigen receptor for chemokines (DARC) and TNBC subtype will be explored for the first time.
Fresh frozen TNBC tissue from the African Research Group for Oncology (ARGO) and Dalhousie/NSHA breast cancer biobanks' will be processing and analyzed by the Genomics Core Facility at Dalhousie University. Clinical data is prospectively collected with specimen acquisition in the ARGO biobank. For the Dalhousie /NSHA biobank, clinical data will be retrospectively gathered from the medical record and migrated to an electronic database for prospective collection during the course of the study. Both cohorts of specimens will be run through DNA and whole transcriptome (mRNA) sequencing on the TSO500 platform (Illumina Ulc.). The tumor-immune microenvironment will be compared between cohorts and by mRNA cluster using the transcriptional signatures for 22 leukocyte populations and immune-regulating proteins CTLA-4 and PD-L1. Finally, tumor expression of DARC will be generated from the transcriptome data that will allow for an assessment of the relationship between DARC expression, TNBC mRNA clusters, and sociodemographic variables (i.e. race/ancestry, gender). Whole transcriptome data from The Cancer Genome Atlas will be pulled as the third cohort, including 55 TNBC specimens from African Americans.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
- Diagnosed with Triple-negative breast cancer
- No diagnosis of Triple-negative breast cancer
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Nova scotia TNBC cohort DNA and whole transcriptome mRNA sequencing DNA and whole transcriptome mRNA sequencing, including total mutational burden and microsatellite instability, will be performed using the TruSight Oncology 500 (TSO500) platform (Illumina Canada, Ulc). Transcriptome data will be used to categorize specimens into one of four distinct mRNA subgroups and will be compared between cohorts. Nigerian TNBC cohort DNA and whole transcriptome mRNA sequencing DNA and whole transcriptome mRNA sequencing, including total mutational burden and microsatellite instability, will be performed using the TruSight Oncology 500 (TSO500) platform (Illumina Canada, Ulc). Transcriptome data will be used to categorize specimens into one of four distinct mRNA subgroups and will be compared between cohorts.
- Primary Outcome Measures
Name Time Method DNA and mRNA sequencing 3 years Duffy-antigen receptor for chemokines 3 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Nova Scotia Health
🇨🇦Halifax, Nova Scotia, Canada