Abstract PR03: Investigation of transcriptome differences in breast cancer tissues from African American and East African patients with triple-negative breast cancer.

Abstract

Abstract Introduction: Strong epidemiological data supports breast cancer (BC) as the second leading cause of cancer death among African-American (AA) women, with a 20% greater mortality rate than that in Caucasians (Cauc). Collection of similar BC incidence and mortality data for Eastern Africa is limited, with the Nairobi Cancer Registry serving as the primary data collection source. However, it is known that in this African region, BC presents as an advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone responsive. Objectives: Our combined investigative team is studying a cohort of indigenous Kenyan breast cancer patients, in order to begin to understand biological similarities and differences between BC in native African and US African patients. Recent gene expression studies conducted by our group suggest differential expression patterns in Triple Negative Breast Cancer (TNBC) across a stage-matched multi-ethnic US cohort. We are extending this focus to similar studies involving native African samples. Methods: Archived BC pathology samples (FFPE) were either obtained from University of Miami (C. Gomez; M. Jorda) or from a native African tumor bank (P. A. Bird, Kijabe). Forty-seven BC samples were contributed from Kenya, and re-analyzed (in Miami) for ER/PR/ Her2Neu status, resulting in confirmation of 29 Kenyan TNBC cases. As expected, a high percentage of the Kenyan tumors were advanced stage and high grade. These Kenyan TNBC cases, as well as US AA TNBC cases from Miami, were analyzed by gene expression studies. 10 um sections were cut from each tumor FFPE block, and following RNA isolation and cDNA preparation, hybridized to the Almac breast-enriched gene expression array (Breast Cancer DSA Research Tool). After quality control assessment of array data, unpaired student's T-test was performed between Kenyan and AA samples, and resulting p-values were corrected for Multiple Testing using Benjamin-Hochberg. Results: Three sets of differentially expressed genes/probes were extracted using different thresholds: Stringent (P-value ≤ 0.01 & Fold Change ≥ 2.0; 1013 probes); Less Stringent (P-value ≤ 0.02 & Fold Change ≥ 2.0; 1669 probes); and Most Significant (P-value ≤ 0.001 & Fold Change ≥ 1.5,136 probes), the latter of which generated hierarchical clustering of the most significant differentially expressed genes. These probe/gene lists were further analyzed using GeneGo pathway analysis. Initial analyses point to possible gene expression differences within several key pathways, including signal transduction in the AKT signaling pathway. Further data set analyses are being performed, including consideration of additional tumor characteristics. The latest data interpretations will be presented. Conclusions: This study represents the first direct comparison of gene expression in TNBC specimens across US AA and Kenyan East Africans. These results will be compared with data from our previous ethnic cohort studies. 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. Ultimately, this work will contribute to our further biologic understanding of BC across different ethnicities, and thus, development of new preventive, predictive and therapeutic measures. This abstract is also presented as Poster B67. Citation Format: Lisa Baumbach, Mark Pegram, Carmen Gomez, Biju Issac, Jennifer Clarke, Merce Jorda, Mary Ellen Ahearn, John Carpten, Peter Bird. Investigation of transcriptome differences in breast cancer tissues from African American and East African patients with triple-negative breast cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PR03.