title: Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease-free survival.
abstract: OBJECTIVE
  We examine prospectively whether the presence of plasma DNA with tumor characteristics before mastectomy is a predictive factor related to recurrence and disease-free survival (DFS).
  
  
  METHODS
  A series of 147 patients with breast carcinomas, selected sequentially, was analyzed. The characterization of plasma DNA, based on similar alterations in tumor and plasma DNA, was achieved with six polymorphic markers (D17S855, D17S654, D16S421, TH(2), D10S197, and D9S161) and mutations in the TP53 gene. Recurrence, DFS, overall survival, and 12 other clinicopathological parameters were obtained. Univariate and Cox's multivariate studies were performed.
  
  
  RESULTS
  A total of 142 patients were eligible for study. A total of 104 tumors (73.2%) showed at least one molecular alteration. In 61 patients (42.9%), a similar molecular alteration was detected in plasma DNA and tumor DNA. No alterations were found in the plasma DNA of the remaining 81 patients (57%). During the follow-up period (median, 22 months; range, 1-46 months), we observed 23 recurrences (16%), the distribution of which was significantly different (P = 0.005) with regard to plasma DNA [17 patients (74%) with circulating tumor DNA and 6 patients (26%) without tumor plasma DNA]. Univariate statistical analysis confirmed the prognostic significance of the already known parameters (tumor size, lymph node metastases, and stage) and demonstrated that tumor plasma DNA was a predictor of DFS. In multivariate analysis, an independent borderline significance was observed for tumor plasma DNA.
  
  
  CONCLUSIONS
  Tumor DNA in plasma at diagnosis in breast cancer patients can predict DFS, and its determination could be used as a prognostic factor in these patients.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, E-28035 Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Silva
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: Antonio
authors.initials: A
authors.lastname: Sanchez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garcia
authors.forename: Gemma
authors.initials: G
authors.lastname: Dominguez
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Luis
authors.initials: L
authors.lastname: Sanfrutos
authors.forename: Eugenia
authors.initials: E
authors.lastname: Jareño
authors.forename: Antonio
authors.initials: A
authors.lastname: Colas
authors.forename: Pilar
authors.initials: P
authors.lastname: España
authors.forename: Felix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008408:Mastectomy; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers