title: The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy.
abstract: BACKGROUND
  The aim of this study was to gain insight into breast cancer dormancy by examining different measures of minimal residual disease (MRD) over time in relation to known prognostic factors.
  
  
  METHODS
  Sixty-four primary breast cancer patients on follow-up (a median of 8.3 years post surgery) who were disease free had sequential bone marrow aspirates and blood samples taken for the measurement of disseminated tumour cells (DTCs), circulating tumour cells (CTCs) by CellSearch and qPCR measurement of overlapping (96-bp and 291-bp) amplicons in circulating free DNA (cfDNA).
  
  
  RESULTS
  The presence of CTCs was correlated with the presence of DTCs measured by immunocytochemistry (P=0.01) but both were infrequently detected. Increasing cfDNA concentration correlated with ER, HER2 and triple-negative tumours and high tumour grade, and the 291-bp amplicon was inversely correlated with DTCs measured by CK19 qRT-PCR (P=0.047).
  
  
  CONCLUSIONS
  Our results show that breast cancer patients have evidence of MRD for many years after diagnosis despite there being no overt evidence of disease. The inverse relationship between bone marrow CK19 mRNA and the 291-bp amplicon in cfDNA suggests that an inverse relationship between a measure of cell viability in the bone marrow (DTCs) and cell death in the plasma occurs during the dormancy phase of breast cancer.
authors.affiliation: Division of Cancer, Imperial College, MRC Cyclotron Building, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Payne
authors.forename: N L
authors.initials: NL
authors.lastname: Hava
authors.forename: K
authors.initials: K
authors.lastname: Page
authors.forename: K
authors.initials: K
authors.lastname: Blighe
authors.forename: B
authors.initials: B
authors.lastname: Ward
authors.forename: M
authors.initials: M
authors.lastname: Slade
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: D S
authors.initials: DS
authors.lastname: Guttery
authors.forename: S A A
authors.initials: SA
authors.lastname: Zaidi
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
authors.forename: J
authors.initials: J
authors.lastname: Jacob
authors.forename: E
authors.initials: E
authors.lastname: Yagüe
authors.forename: J A
authors.initials: JA
authors.lastname: Shaw
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D004247:DNA