Abstract A38: Identification of triple-negative breast cancer subtypes in Colombian patients
Authors: Serrano-Gomez Silvia J. , Sanabria-Salas Maria Carolina , Garai Jone , Baddoo Melody C. , Hernandez-Suarez Gustavo , Mejia Juan Carlos , Garcia Oscar , Miele Lucio , Fejerman Laura , Zabaleta Jovanny 
Published: February 2019

Background: Studies in Latinas have reported a high prevalence of ER/PR/HER2-negative (TNBC) and HER2-enriched breast tumors. In our ongoing study of breast cancer molecular characteristics of Colombian women (N=301), more than 20% of the tumors were classified as TNBC. Molecular analyses of this aggressive subtype of breast cancer in women of European ancestry have revealed additional molecular heterogeneity, which is associated with treatment response and survival. The goal of the present study was to explore the molecular profile of TNBC in a sample of Latin American women from Colombia and assess if genetic ancestry modified the gene expression profile.

Methods: We performed whole-transcriptome RNA-seq analysis in 48 TNBC tumors that were classified into intrinsic subtypes by immunohistochemistry (IHC) following St. Gallen 2015 surrogates. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients with TNBC according to the median of Indigenous ancestry (low Indigenous ancestry group: ancestry proportion below the median; high Indigenous ancestry: ancestry proportion above the median). We used top differentially expressed genes from Lehmann et al. (2011) (n=128) to explore the distribution of TNBC subtypes in our samples and to explore differences in the expression of these genes according to genetic ancestry.

Results: Unsupervised hierarchical clustering analysis did not show any clear clustering of the Colombian samples into defined subtypes based on expression of the 128 top differentially expressed genes reported by Lehmann et al. Subsequently, we selected genes that clustered together according to the definitions of TNBC subtypes of Lehmann, leaving a total of 35 genes for the analysis. Unsupervised hierarchical clustering using this list of genes identified two clusters, one predominantly observed for woman of high Indigenous American ancestry (average Indigenous American ancestry for this group was 45%) and another more common in women of low Indigenous ancestry (average Indigenous American ancestry for this group was 36%, p=0.04). The cluster that included most of the women with high Indigenous ancestry proportions was characterized by lower gene expression for the 35 genes compared to the cluster that included women with low Indigenous ancestry proportions.

Conclusions: Our results suggest differential expression of genes within TNBC breast cancer subtype according to genetic ancestry; nevertheless, we could not identify clear TNBC subtypes previously defined by Lehmann et al. in our study. Further analyses are needed to identify TNBC subtypes in Hispanic/Latina samples.

Citation Format: Silvia J. Serrano-Gomez, Maria Carolina Sanabria-Salas, Jone Garai, Melody C. Baddoo, Gustavo Hernandez-Suarez, Juan Carlos Mejia, Oscar Garcia, Lucio Miele, Laura Fejerman, Jovanny Zabaleta. Identification of triple-negative breast cancer subtypes in Colombian patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A38.