Abstract 172: Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing

Abstract

Abstract Background: Metastatic breast cancer (MBC) is an incurable disease with complex molecular features including somatic mutations that evolve in relation to genomic instability and selective treatment pressure. Patients with treatment-refractory MBC may benefit from tumor genomic evaluation using next generation sequencing (NGS). Furthermore, analysis of circulating tumor DNA (ctDNA) in patients with advanced disease offers the possibility of non-invasive molecular monitoring. Methods: A patient with MBC was tested at each progression with a ctDNA NGS panel (Guardant360™) that includes all NCCN-recommended somatic genomic variants for solid tumors and sequences complete exons of >50 genes to report single nucleotide variants (SNVs), fusions, amplifications, and indels with high sensitivity and ultra-high specificity (>99.9999%). The patient was diagnosed with invasive breast cancer at age 44 and treated with surgery and hormonal therapy. At age 61, she had axillary adenopathy and liver metastases. Treatment details are in Table 1. Results: ctDNA analysis was performed at the time of metastatic diagnosis and at 5 additional time points over the course of treatment. All samples revealed an ERBB2 exon 19 indel (p.Leu755_Glu757delinsSer), and multiple SNVs and gene amplifications. ERBB2 amplification was seen in 4 of 6 samples. Mutant allele fractions (Table 1) correlated with clinical response to treatment and progression. Conclusions: Analysis of ctDNA in this patient identified an ERBB2 exon 19 indel, which are present in 2-4% of non-small cell lung cancers but 1-2% in breast cancer. Treatment with anti-HER2 monoclonal antibody or dual anti-EGFR/ERBB2 tyrosine kinase inhibitor therapies may show clinical benefit. ctDNA analysis can detect emergence of actionable resistance mutations with the advantage of serial evaluation, allowing capture of inter- and intra-tumor heterogeneity and illustration of molecular progression and response. Table 1.Blood DrawDisease status at time of blood drawMutant allele fraction of ERBB2 indel (* = ERBB2 amplification)Treatment1Initial diagnosis9%trastuzumab, pertuzumab and docetaxel (TPD), cycle 12Stable disease1%*TPD cycle 23Progressing10%*TPD cycle 34Progressing62%*trastuzumab, emtansine (TDM1) 3 cycles5Progressing70%*vinorelbine, trastuzumab, everolimus6Partial response1%flourouracil, epirubicin, cyclophoasphamide Citation Format: Laura Austin, Rebecca Nagy, Oliver Zill, Richard B. Lanman, AmirAli Talasaz, Massimo Cristofanilli. Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 172.