TRACER - ctDNA evaluation in early breast cancer

Aims/Goals:

  1. Define an optimal high sensitivity ctDNA assay for women with early breast cancer. 

  1. Prospectively characterize ctDNA tumor dynamics and resistance profiling throughout standard therapy for women with early stage breast cancer receiving NAC. 

  1. Evaluate ctDNA dynamics in relation to clinical, pathologic (pCR/PR/NR), and standard diagnostic imaging correlates.

Summary:

In Canada, breast cancer (BC) is the second highest cause of cancer related mortality in women. Five-year survival rates approximate 87% but vary widely by age, ethnicity, and stage at diagnosis. Previous improvements in survival reflect the implementation of population level screening and advances in adjuvant therapy. Progress is now limited by diagnostic sensitivity that can detect local or disseminated micro-metastases5 in patients destined for recurrence to allow early intervention. 

Circulating tumor DNA (ctDNA) is a real-time, cancer biomarker that can provide non-invasive diagnostic and prognostic information during cancer treatment and upon relapse. Their utility in the detection of residual disease and evaluation of mutational burden have been described in recent publications. Novel approaches such as methylated ctDNA immunoprecipitation protocol (cfMeDIP-seq) optimized at Princess Margaret (PM) by De Carvalho et. al to standardized CAPP-seq assays could yield significant advantages including 1) epigenetic methylation analysis, 2) methylation specific tumor identification, 3) low input thresholds (10 ng DNA) and, 4) indifference to somatic mutations. 

Key Researchers