Molecular Subtyping of Triple-negative Breast Cancer and African Ancestry-related Immunogenicity

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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Genetic: DNA and whole transcriptome mRNA sequencing

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.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B2Y 1A7
      • Nova Scotia Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Biological samples acquired from patient's with Triple-negative breast cancer

Description

Inclusion Criteria:

• Diagnosed with Triple-negative breast cancer

Exclusion Criteria:

• No diagnosis of Triple-negative breast cancer

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Nova scotia TNBC cohort; 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.	Genetic: 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).
Nigerian TNBC cohort; 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.	Genetic: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DNA and mRNA sequencing	3 years
Duffy-antigen receptor for chemokines	3 years

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Collaborators: Obafemi Awolowo University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 42127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No