(ChemotherapyAdvisor) – The first direct comparison of gene expression in triple-negative breast cancer (TNBC) tissue specimens from US African American and Kenyan East African women has found differences within several key pathways, including AKT signal transduction, investigators reported during the Fifth AACR Conference on The Science of Cancer Health Disparities, San Diego, CA.
“Ultimately, this work will contribute to our further biologic understanding of breast cancer across different ethnicities, and thus, development of new preventive, predictive, and therapeutic measures,” noted Lisa Baumbach-Reardon, PhD, of the Translational Genomics Research Institute (TGen), Phoenix, Arizona.
The investigators are studying a cohort of indigenous Kenyan women with breast cancer to understand biological similarities and differences between breast cancer in native African and US African patients.
Archived breast cancer pathology samples were obtained from the University of Miami or from the Nairobi Cancer Registry. Of the 47 samples from Kenya reanalyzed in Miami for ER/PR/Her2neu status, 29 cases of TNBC were confirmed. “As expected, a high percentage of the Kenyan tumors were advanced stage and high grade,” Dr. Baumbach-Reardon said.
The Kenyan and US African American cases of TNBC were analyzed by gene expression studies and three sets of differentially expressed genes/probes extracted using different thresholds, she reported. “Stringent” was defined as P-value ≤0.01 and a fold change ≥2.0 (1013 probes); “less stringent” as P-value ≤0.02 and fold change ≥2.0 (1669 probes); and “most significant”, as P-value ≤0.001 and fold change ≥1.5 (136 probes).
The “most significant” threshold “generated hierarchical clustering of the most significant differentially expressed genes,” she reported. When these probe/gene lists were analyzed using GeneGo pathway analysis, possible gene expression differences were observed within several key pathways, including signal transduction in the AKT signalling pathway. Chromosomal aberrations and variants in a subset of the Kenyan samples were also explored.
The researchers do not yet fully understand why TNBC is overrepresented in women of African descent, although it is clear multiple factors play a role, Dr. Baumbach-Reardon noted. “We will strive to correlate all experimental data with available clinical data, and determine possible correlations between genomic signatures, clinical tumor characteristics, and demographic information among and across ethnic groups,” she concluded.