Abstract 4844: Genomics aberrations and BRCA1 silencing in hereditary triple negative breast tumors in Chilean women

Abstract

Abstract Breast cancer is one of the most common cancers in women worldwide and the second cause of death by cancer among women in Chile. Either sporadic or hereditary breast cancers show a wide variety of tumor phenotypes, leading to individual clinic responses to specific treatments. Among breast cancer tumors, a group named as triple negative breast cancer (TNBC) does not express hormone receptors and HER2 (ER-, PR-, HER2-). For these tumors no specific treatment complementing chemotherapy has been developed yet. Therefore the study of the genes involved in the progression of TNBC tumor may provide a rationale for the future exploration of therapeutic strategies. TNBC is frequently observed in women carrying a germline mutation in the BRCA1 gene and in approximately 30% of non-carrier women with loss of expression of BRCA1 protein. Our aim, is to identify common genomic aberrations among TNBC tumors and to evaluate BRCA1 silencing by hypermethylation of its promoter in TNBC tumors. It has been described that about 80-90% of TNBC tumors belong to the basal-like molecular subtype, constituting a biological and clinical distinct subgroup. To determine the basal-like subtype we evaluated the expression of Cytokeratin 14 (CK14) marker in 22 hereditary TNBC. Our results revealed that a 63% (14/22) of the tumors express CK14, suggesting that these tumors belong to the basal-like subtype. Additionally, we analyzed the methylation status of the BRCA1 promoter and its correspondent protein expression in the tumors. A 77% (17/22) of the tumors had BRCA1 promoter hypermethylation. Of all tumors 32% (7/22) had absent or reduced nuclear expression of BRCA1. Interestingly, we found 54% (12/22) of the TNBC tumors with a cytoplasmic expression of BRCA1. Finally, we also analyzed through array-CGH, 19 hereditary TNBC tumors to identify common genomic aberrations between these tumors. The array-CGH analysis revealed the gain of the genomic regions 7q34, 15q26.1 and 16p13.3 and the deletion of the regions 1q21.1, 9q33.3, 18q22.1-q22.3 and 19q13.41 in more than 30% of the TNBC tumors. In conclusion, we found that 71% of tumors expressing CK14 have absent or reduced expression of the BRCA1. On the other hand, 61% of tumors with promoter hypermethylation of BRCA1 have loss expression of its protein. Interestingly, the region deleted 1q21.1 was found in 94% of the hereditary TNBC tumors. Financed by FONDECYT 1080595 and CONICYT 24091058. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4844. doi:10.1158/1538-7445.AM2011-4844