Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer

Nat Commun. 2015 Nov 4;6:8760. doi: 10.1038/ncomms9760.

Abstract

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bayes Theorem
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Case-Control Studies
  • Clonal Evolution / genetics*
  • DNA, Neoplasm / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Humans
  • Lapatinib
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / secondary
  • Mutation
  • Neoplasm Metastasis
  • Quinazolines / administration & dosage
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Sequence Analysis, DNA
  • Spinal Neoplasms / genetics*
  • Spinal Neoplasms / secondary
  • Tamoxifen / administration & dosage
  • Trastuzumab / administration & dosage

Substances

  • DNA, Neoplasm
  • Quinazolines
  • Receptors, Estrogen
  • Tamoxifen
  • Lapatinib
  • Deoxycytidine
  • gemcitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab