Abstract PD05-01: Next generation genomic sequencing (NGS) identifies molecular targets in inflammatory breast cancer (IBC)

Abstract

Abstract BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of invasive breast cancer and is associated with poor outcome in spite of optimal multidisciplinary management. The disease is associated poor response to neoadjuvant chemotherapy and a peculiar pattern of recurrence (chest wall, nodes, CNS). There currently few distinct molecular alterations for effective therapeutic targeting in the advance setting. The availability of comprehensive cancer genomic testing using Next-Generation Sequencing (NGS) technology may identify a number of genomic alterations not assessed by traditional methods and provide opportunities for more effective treatment selection particularly in aggressive and uncommon diseases such as IBC. METHODS: Twenty-three patients with refractory metastatic IBC were included in this analysis. All patients underwent confirmatory biopsy and/or tissue collection. Tissue from metastastic lesions of patients with recurrent IBC was submitted as slides or FFPE blocks. NGS was performed by Foundation Medicine, Cambridge, MA. The entire coding sequence of 182 cancer-related genes (3,230 exons) plus 37 introns from 14 genes often rearranged in cancer were sequenced to high depth (>500X) All classes of genomic alterations were detected. RESULTS: The site distribution and frequency of disease recurrence included: soft tissue (19) lung (4), bone and liver (3), and brain (2). The disease subtype classification based on the expression of ER, PR and HER-2 were as follow: ER−, PR−, Her-2−, Basal-like or TN (65%); ER+ and/or PR+, HER-2− (grade3) or HER-2+, Luminal B (22%); ER−, PR−, HER2+ (13%). Genomic alterations were identified in all patients with various frequencies. Genetic mutations included: P53 (DNA-binding domain, splice site), PI3KCA (H1047R, R441N, E545K, K111E,); RB1; PTEN (D107Y); EGFR (L858R); ERBB2 (V777L, S310F) in a patient with TN disease; ESR1 D538G. Gene amplifications included: MYC (26%); CCND1 (22%); ERBB2 (in a patient with TN disease), MLC-1, CCNE1, CK4, K-RAS. One patient had evidence of discordant genomic abnormalities in two simultaneous sites of recurrence (skin and pleura) suggesting disease heterogeneity. Three patients were effectively treated with genomic alterations-guided therapies. CONCLUSIONS: Genomic sequencing of advanced IBC is feasible, identifies potential therapeutic targets and can advance our understanding of the molecular alterations of this aggressive disease. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-01.