171O - Monitoring of metastatic breast cancer using circulating tumour DNA: a comparison with circulating tumour cells

Date 29 September 2012
Event ESMO Congress 2012
Session Biomarkers in breast and colorectal cancer
Topics Biomarkers
Breast Cancer, Metastatic
Presenter Sarah-Jane Dawson
Authors S. Dawson1, D. Tsui2, M. Murtaza2, H. Biggs3, S. Chin2, D. Gale2, T. Forshew2, M. Wallis4, N. Rosenfeld2, C. Caldas1
  • 1Department Of Oncology, Li Ka Shing Centre, Cancer Research UK, Cambridge Research Institute Addenbrooke's Hospital, CB2 0RE - Cambridge/UK
  • 2Oncology, Li Ka Shing Centre, Cancer Research UK, Cambridge Research Institute Addenbrooke's Hospital, CB2 0RE - Cambridge/UK
  • 3Oncology, Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ - Cambridge/UK
  • 4Department Of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ - Cambridge/UK

Abstract

Background

Management of metastatic breast cancer (MBC) requires monitoring of tumour response to determine treatment efficacy. Imaging is routinely used, but is often a poor indicator of dynamic clinical response. Circulating tumour cells (CTCs) have been extensively studied but dynamics of cell-free DNA carrying tumour-specific alterations (circulating tumour DNA, ctDNA) has only recently been demonstrated. We performed the first direct comparison of CTCs and ctDNA in relation to medical imaging, to compare the performance of these biomarkers for the non-invasive monitoring of MBC.

Methods

Clinical details, imaging and serial whole blood were collected prospectively from women undergoing therapy for MBC. DNA from tumour tissues was analysed using targeted and/or whole genome sequencing to identify somatic genetic alterations. These were used to design personalised assays to quantify ctDNA in plasma using digital PCR. CTCs were quantified at identical time points using the CellSearch® system. A blinded review of all imaging was performed according to RECIST criteria.

Results

Concurrent CTC and ctDNA data was available from 16 women across 58 samples. Elevated CTCs (≥5 cells / 7.5ml blood) and ctDNA were identified in 11 (69%) and 15 (94%) cases respectively. ctDNA levels were a median of 234-fold higher than CTC numbers and showed greater sensitivity for monitoring tumour dynamics. In several cases, rising ctDNA was identified months before progressive disease was detected by CTCs or imaging. Changes in ctDNA levels were also observed in a subset of women with no measurable disease using the other modalities. Multiple somatic mutations and structural variants were measured in parallel in ctDNA, demonstrating the utility of this methodology to follow clonal evolution during treatment.

Conclusions

ctDNA is a more sensitive biomarker than CTCs for the monitoring of MBC and often provides the earliest measure of treatment response. ctDNA has the potential to be used as a ‘liquid biopsy’ to directly monitor responses to targeted therapies and detect the emergence of resistant mutations. Future work should focus on the integration of ctDNA monitoring into multi-centre prospective clinical trials.

Disclosure

All authors have declared no conflicts of interest.