Abstract PO-220: Comprehensive "omic" portraits of breast cancer in Mexican-Hispanic women

Breast cancer is a relevant public health problem that affects millions of women worldwide. Breast tumors are recognized as a clinically and molecular heterogeneous pathology, but the genomic basis of its variability remains poorly understood, mainly regarding the comprehensive of ethnicity/racial disparities and their consequences in genomics studies. Moreover, most of the comprehensive molecular characterizations are predominantly centered on Caucasian population. Thus, we deeply characterized the molecular architecture of breast cancer in a set of Mexican patients through genomic and transcriptomic portraits. We explored the molecular features of breast cancers in Mexican-Hispanic (HM) women and compared them with public multi-ethnic datasets. HM patients presented an earlier onset of the disease, in particular in the aggressive Basal-like/triple negative and Luminal B subtypes. The significant E17K hotspot mutation in AKT1 gene occurred in 8% of the HM tumors, an enriched prevalence exclusively seen in this dataset. An integrative analysis also revealed an important role of the AKT1/PIK3CA axis as a potentially druggable target and indicate an aggressive biology. Computational analysis allowed us to identify age-related COSMIC (v2) signature 1 to be present in a much broader spectrum of HM women than in those from other ethnicities. On the basis of transcriptome immunogenomic analysis across human population we identified that luminal breast tumors with HM ancestry presented an enhanced immunogenic phenotype than their Asiatic and Caucasian counterparts. To the best of our knowledge, this dataset represents the largest breast cancer genomics characterization of breast tumors in Mexican women, and, provides novel insights into molecular phenotypes and mechanisms underlying carcinogenesis in a group of Mexican Hispanic women. In conclusion, this study provides a conceptual framework to better understand ethnic disparities of breast cancer.

Citation Format: Sandra Lorena Romero-Cordoba, Ivan Salido-Guadarrama, Rosa Rebollar-Vega, Alberto Tenorio-Flores, Verónica Bautista-Piña, Felipe Villegas-Carlos, Carlos Dominguez-Reyes, Alfredo Hidalgo-Miranda. Comprehensive "omic" portraits of breast cancer in Mexican-Hispanic women [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-220.