92O - The Breast International Group (BIG) AURORA pilot study for molecular screening in metastatic breast cancer (MBC) patients

Date 08 May 2015
Event IMPAKT 2015
Session Mutations and therapy resistance: Impact of mutations in the clinic
Topics Breast Cancer
Translational Research
Presenter Marion Maetens
Citation Annals of Oncology (2015) 26 (suppl_3): 31-33. 10.1093/annonc/mdv121
Authors M. Maetens1, A. Irrthum2, S. Loibl3, J.F. Laes4, P. Campbell5, P. Aftimos6, A. Thompson7, J. Cortes Castan8, S. Loi9, C. Sotiriou10
  • 1Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 2Bioinformatics, Breast International Group, 1000 - Brussels/BE
  • 3Na, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 4Na, OncoDNA, Gosselies/BE
  • 5Cancer Genetics And Genomics, Wellcome Trust Sanger Institute, Cambridge/UK
  • 6Medical Oncology, Institute Jules Bordet, Brussels/BE
  • 7Surgical Oncology, MD Anderson Cancer Center, Houston/US
  • 8Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 9Na, Peter MacCallum Cancer Center, Melbourne/AU
  • 10Head Of Breast Cancer Translational Research Laboratory, Institut Jules Bordet, 1000 - Brussels/BE

Abstract

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Introduction: In 2014, the BIG set up the AURORA molecular screening program for patients with MBC. Before launching the project, a pilot study was initiated with the primary aim to investigate feasibility in terms of logistics and timelines. Secondary aims were to compare somatic mutation calls between two targeted gene sequencing (TGS) platforms and somatic copy number aberrations (SCNA) calls obtained from TGS and single nucleotide polymorphism (SNP) oligonucleotide arrays.

Methods: MBC patients were enrolled in 4 European centers. Eligibility criteria for TGS were: 1) at least one representative metastatic biopsy, 2) availability of a whole blood sample and 3) >10% tumor cellularity at central pathological review. Tumor and normal DNA were subjected to TGS of cancer related genes using the Ion Torrent and Illumina platforms. SCNA calls obtained from normalized coverage of TGS data were compared to the output of the ASCAT algorithm on Affymetrix OncoScan FFPE array data.

Results: Forty-one patients were enrolled and 35 of them were biopsied (85%). Successful TGS results were obtained for 26/35 patients (74%). The most common biopsied metastatic sites were the liver (43%) followed by breast (20%), lymph node (14%), skin (14%), lung (6%) and bone (3%). The tumor cellularity ranged from 10 to 85%. The median turnaround time to report the TGS results was 9 working days (range: 5-17). Somatic mutations were called in exons covered at >100X based on a fixed threshold of 10% variant allele frequency in the cancer sample. The median number of mutations per patient identified from Ion Torrent, was 7 (range: 0-29), with 60% of the patients harboring at least one “actionable” mutation. Preliminary results show a validation rate of 68% (range: 33-100%) from Ion Torrent by Illumina. The SCNAs are currently being analyzed and will be presented at the IMPAKT conference.

Conclusion: This pilot study demonstrates the feasibility of conducting an international MS program for MBC patients in routine clinical settings. The mutation calls validation rate was deemed acceptable. Collectively, these results are reassuring for the conduct of AURORA, aiming at recruiting 1300 patients with MBC from more than 80 European sites.

Disclosure: All authors have declared no conflicts of interest.