Abstract 144P
Background
Currently, routine surveillance after primary therapy of early Breast cancer (BrCa) is limited to breast imaging. Follow up surveillance using circulating tumour DNA (ctDNA) for the detection of molecular residual disease is a useful tool to identify patients who may eventually develop distant metastases and holds promise for earlier intervention and improved overall survival. However, genomic alternations in breast cancer are very heterogeneous and follow-up surveillance requires ultrasensitive ctDNA assays. Here we evaluate RaDaRTM, a personalised sequencing assay for residual and recurrent disease detection after standard treatment in early-stage BrCa.
Methods
37 early-stage BrCa patients recruited through the BRandO BiO registry study were included. Whole exome sequencing (WES) was performed on FFPE tumor tissue from curative-intent surgery and variants selected for RaDaR panels (38-54 variants/panel; median: 49). The RaDaR assay was used to analyze plasma samples from 21 patients with confirmed clinical progression after median 1.5 years and 16 case-control patients who had not experienced a recurrence at the time of 3-year follow-up. All samples analysed were blinded to outcome.
Results
ctDNA was detected in 71% of patients (15/21) with confirmed clinical recurrence (12 with distant and 3 with local recurrence), at an estimated median variant allele frequency (VAF) of 0.069% (range 0.0029% to 2%). Patients with locaI recurrence had the lowest ctDNA levels (0.0029%, 0.0146% and 0.0248% VAF). Of the remaining 6 patients with recurrence but negative for ctDNA, 5 had local and one distant recurrence with unusual histology, indicating an alternative origin or a second primary. Only 1 of 16 control patients without documented clinical recurrence was ctDNA positive, albeit at low detection levels (0.0085% VAF), potentially indicating presence of early recurrence that precedes clinical diagnosis.
Conclusions
In this pilot study, the RaDaR assay detected the presence of ctDNA in plasma to levels as low as 0.0029% VAF. We found that sensitive detection of disease with this assay was strongly associated with distant recurrence in early-stage BrCa, with 12 of 13 cases detected.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital Ulm.
Funding
Bundesministerium für Bildung und Forschung, within the first call of the Dekade gegen Krebs.
Disclosure
C. Pipinikas: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. V. Müller: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar; Financial Interests, Personal, Advisory Role: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro and Nektar; Non-Financial Interests, Personal, Other: Novartis, Roche, Seattle Genetics, Genentech. G. Marsico: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. P. Freire-Pritchett: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. C. Knape: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. K. Howarth: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. K. Pantel: Financial Interests, Personal, Other: Menarini, Illumina, and Agena; Financial Interests, Personal and Institutional, Funding: European IMI research project CANCER-ID (115749-CANCER-ID), European Union Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie grant agreement No 765492 and ERA-NET EU/TRANSCAN 2 JTC 2016 PROLIPSY. K.P. also received funding from. N. Rosenfeld: Financial Interests, Personal, Full or part-time Employment: Inivata; Financial Interests, Personal, Stocks/Shares: Inivata. All other authors have declared no conflicts of interest.