title: Circulating tumor cells and plasma DNA analysis in patients with indeterminate early or metastatic breast cancer.
abstract: BACKGROUND
  Circulating tumor cells (CTCs) and tumor-specific alterations in cell-free plasma DNA can both be used as markers of prognosis in breast cancer. To date, there have been no studies that have compared these as markers for subclinical metastases in the follow-up of early breast cancer. In this study, we measured CTCs and plasma DNA in a published group of patients with multiple pulmonary nodules and indeterminate metastatic disease.
  
  
  METHODS
  A single blood sample for CTC and plasma DNA measurement was taken approximately 1.5 years after surgery from 19 women with histologically confirmed primary breast cancer and small pulmonary nodules. The CellSearch system was used to enrich and enumerate CTCs from peripheral blood. DNA was isolated from plasma and was analyzed by quantitative real-time PCR for DNA concentration, integrity and evidence of HER2 amplification.
  
  
  RESULTS
  Of the 19 individuals with 'indeterminate' early or metastatic breast cancer, 17 demonstrated no evidence of CTCs, one had one CTC and one had three CTCs. The mean plasma DNA concentration was low and within the range detected in healthy female controls, as were the values for DNA integrity. HER2 amplification was detected in the plasma DNA in four of the eight patients with HER2 immunohistochemistry 3+ tumors, but there was no overlap with the two CTC-positive patients. None of the patients have relapsed thus far (median follow-up: 3.5 years).
  
  
  CONCLUSIONS
  Both CTC and plasma DNA analyses together suggested that these patients had little evidence of metastatic disease. Future studies will be designed to assess the utility of these biomarkers in the follow-up of a larger number of women with breast cancer.
authors.affiliation: Department of Cancer Studies & Molecular Medicine, University of Leicester, Leicester Royal Infirmary, UK.
authors.forename: Jacqui A
authors.initials: JA
authors.lastname: Shaw
authors.forename: James
authors.initials: J
authors.lastname: Brown
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jacob
authors.forename: Rachel
authors.initials: R
authors.lastname: Payne
authors.forename: Belinda
authors.initials: B
authors.lastname: Lee
authors.forename: Karen
authors.initials: K
authors.lastname: Page
authors.forename: Natasha
authors.initials: N
authors.lastname: Hava
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000097:blood*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D055613:Multiple Pulmonary Nodules / Q000556:secondary; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA; D018719:Erb-b2 Receptor Tyrosine Kinases