Abstract
Background: Focal amplification of fibroblast growth factor receptor 1 (FGFR1) defines a subgroup of breast cancers with poor prognosis and high risk of recurrence. We sought to demonstrate the potential of circulating cell-free DNA (cfDNA) analysis to evaluate FGFR1 copy numbers from a cohort of 100 metastatic breast cancer (mBC) patients. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were screened for FGFR1 amplification by FISH, and positive cases were confirmed with a microarray platform (OncoscanTM). Subsequently, cfDNA was evaluated by two approaches, i.e., mFAST-SeqS and shallow whole-genome sequencing (sWGS), to estimate the circulating tumor DNA (ctDNA) allele fraction (AF) and to evaluate the FGFR1 status. Results: Tissue-based analyses identified FGFR1 amplifications in 20/100 tumors. All cases with a ctDNA AF above 3% (n = 12) showed concordance for FGFR1 status between tissue and cfDNA. In one case, we were able to detect a high-level FGFR1 amplification, although the ctDNA AF was below 1%. Furthermore, high levels of ctDNA indicated an association with unfavorable prognosis based on overall survival. Conclusions: Screening for FGFR1 amplification in ctDNA might represent a viable strategy to identify patients eligible for treatment by FGFR inhibition, and mBC ctDNA levels might be used for the evaluation of prognosis in clinical drug trials.
Highlights
A plethora of genomic alterations, including mutations, amplifications, and gene fusions, have been described for the different members of the fibroblast growth factor receptor (FGFR) family in multiple cancer types [1]
The moderate signs of efficacy could be the cumulative effect of ineffective compounds, The moderate signs of efficacy could be the cumulative effect of ineffective compounds, inadequate inadequate patient selection, the lack ofpotential oncogenic patient selection, or the lack ofor oncogenic of potential
Despite the small sample size, good concordance was concordance was observed between fibroblast growth factor receptor 1 (FGFR1) amplification in plasma assessed from shallow whole-genome sequencing (sWGS) data and observed between FGFR1 amplification in plasma assessed from sWGS data and the tissue-based the tissue‐based analysis
Summary
A plethora of genomic alterations, including mutations, amplifications, and gene fusions, have been described for the different members of the fibroblast growth factor receptor (FGFR) family in multiple cancer types [1]. FGFR1 amplification and protein expression have been demonstrated as an unfavorable prognosis factor [5,8,9,10]. In addition to ER resistance, FGFR1 amplification has been demonstrated to confer broad resistance to PI3K and CDK4/6 inhibitors [11]. Focal amplification of fibroblast growth factor receptor 1 (FGFR1) defines a subgroup of breast cancers with poor prognosis and high risk of recurrence. We sought to demonstrate the potential of circulating cell-free DNA (cfDNA) analysis to evaluate FGFR1 copy numbers from a cohort of 100 metastatic breast cancer (mBC) patients. We were able to detect a high-level FGFR1 amplification, the ctDNA AF was below 1%
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
