WORKPACKAGE 7

Towards using ctDNA and multi-OMICS in active surveillance of DCIS

Hypoptheses

  • Monitoring using ctDNA will improve the sensitivity and/or specificity of surveillance in women who do not have surgery for DCIS
  • ctDNA can provide an early identifier of recurrence (or progression to a higher risk group) in women who have had surgery for DCIS
  • Study of progressive or recurrent lesions can provide important basic information on mechanisms of non-indolent behaviour in DCIS and identify actionable molecular changes

In the PRECISION project we make preparations for ct-DNA and multi-OMICS studies in the future. The prospective LORIS, COMET and LORD randomised trials together present this unique opportunity. They have a common aim of assessing which low or intermediate grade DCIS requires primary surgical management and whether regular monitoring for disease progression by mammography can be safely performed, with intervention only in those women with evidence of progression to high risk DCIS or invasive cancer.

 

In PRECISION up to 900 women taking part in LORIS/COMET/LORD (half from each arm) will be asked to give additional consent to provide

  • access to biopsy showing DCIS at presentation (already consent is provided for this)
  • paired normal DNA sample (from EDTA blood)
  • full clinicopathological data, including baseline immunohistochemistry for ER, PR, ERBB2, basal markers, other markers of cell of origin
  • Streck tube samples of~20ml blood for ctDNA, taken at presentation, and annually thereafter to 5 years (i.e. at the same time point as annual mammography)

Workpackage 7 is responsible for the project objective to collect from all patients in LORIS, LORD and COMET Trials diagnostic tissue and blood from annual mammogram time points

Milestones

7.1 Liquid biopsy sample collection commences on all patients due to annual mammograms in LORIS
7.2 Transfer of diagnostic biopsy tissue for baseline analysis from LORIS, COMET and LORD commences
7.3 Liquid biopsy sample collection on all patients reaching annual mammogram due date in COMET and LORD
7.4 Frozen sample trios collected
7.5 In collaboration with WP4: Prospective sample collection
7.6 In collaboration with WP5:
A collection of well-characterised 3D tumoroids of DCIS (in collaboration with WP5)
A collection of well-characterised genetically engineered mouse models (GEMMs) of DCIS
A collection of well-characterised patient-derived xenograft (PDX) models of DCIS

WP lead

Professor Daniel Rea

Professor of Medical Oncology

University of Birmingham, Birmingham, UK

Collaborators

Dr John Bartlett

Ontario Institute for Cancer Research, Ontario, Canada

 

Professor Sarah Pinder

Kings College, London, UK