Abstract B062: Genetic driving factors of aggressive Ethiopian breast cancer (2020)

Abstract In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. The standard of care for Ethiopian breast cancer patients is radiotherapy and broad-spectrum chemotherapy, which is also the case for US patients with triple-negative breast cancer (TNBC). However, the limited publications that do exist on Ethiopian tumors, and our own preliminary data, suggest that a large proportion of these patients have hormone-positive (ER+) breast cancer. This is surprising 1) given the aggressive nature of the disease, 2) given that African Americans with breast cancer frequently have TNBC, and 3) given the non-hormone targeting treatment these patients are receiving. There is a paucity of information on the molecular and genetic driving factors driving Ethiopian breast cancer, and this is critically hindering treatment strategies for these patients. The Black Lion Hospital in Addis Ababa treats patients from all over the country, and so we have partnered with Dr. Daniel Seifu at the Black Lion Hospital to gather more information about this deadly disease. In this project, we have brought together expertise across multiple institutions to collect tumor specimens, subtype the specimens, and perform DNA and RNAseq on these tumors. We used the TruSeq Exome kit (Illumina) to sequence matched normal and tumor tissue from 3 patients from a small pilot collection. We identified mutations in 127 genes across all three patients, unique to the tumor tissue. We found mutations in BARD1, BRCA2, and BRIP1, and each patient had a mutation in a different spot in the BRCA2 gene. Second, we compared our data to a list of mutations found for inherited breast and ovarian cancer (1), and found mutations in BRCA2, BRIP1, and MSH2, but not the other 7 panel genes. Finally, we compared our initial data set to the Personalized Cancer Mutation Panel (covering 737 mutational hotspots on 45 genes, across many different cancers (2), and found mutations in 3 of these genes: ALK, APC, and HNF1A, but not in the other 42 genes in their panel. At the same time, all these mutations we identified were specific to the tumor tissue and were not found in the matched healthy tissue we analyzed. At this conference we will discuss these results and our analysis from the additional collected samples as the project continues. References 1. Walsh T et al. Proc Natl Acad Sci U S A 2010;107(28):12629-33. 2. Liu S et al. Hum Genomics 2015;9:2. Citation Format: Alyssa Schwartz, Kathryn Bittner, Manu Platt, Daniel Seifu, Sallie Schneider, Patrick Flaherty, Courtney Babbitt, Shelly Peyton. Genetic driving factors of aggressive Ethiopian breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B062.