Grant: Travel Awards - Institute Community Support

Rare breast cancer (BC) histopathological BC subtypes (collectively less than 2% of all breast cancer) have particular prognostic and clinical characteristics. There is no current established treatment that take in account the specificity of rare BC subtypes. This is mainly due to the absence of clinical trials to determine the optimal management of these rare pathologies. The establishment of relevant preclinical models and molecular characterization of rare BC subtypes is essential for identifying directed and suitable therapeutic regimens for BC patients diagnosed with these rare histopathological variants. Patient-derived xenograft (PDX) has been recognized as a valuable method to evaluate the clinical diversity of breast cancer. These models were shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. We developed a cohort of eight BC rare histopathological subtypes, including four metaplastic, one adenoid cystic, one IDC pleomorphic, one neuroendocrine, and one mucinous BC subtype. These PDXs and their primary tumors were submitted to whole genome sequencing (WGS) and RNA sequencing. We also evaluated a total of 255 proteins by reverse phase protein array (RPPA) in these PDXs samples. We are currently performing experiments to generate cell lines from these rare BC PDXs. Our preliminary results indicate that several pathways are dysregulated in rare BC tumors. The genes belonging to these pathways represent potential therapeutic targets for personalized treatment.