title: Circulating plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy.
abstract: BACKGROUND
  In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting response to therapy are urgently required.
  
  
  METHODS
  In 65 patients with locally confined breast cancer who had completed the course of chemotherapy until surgery, plasma DNA biomarkers obtained before and during therapy were evaluated concerning (early) estimation of therapy response. Levels of repetitive ALU 115 and ALU 247 elements as well as DNA integrity calculated according the formulas of Umetani (1) and Wang (2) were correlated with changes in histopathological staging at surgery and compared with conventional tumor markers CEA and CA 15-3.
  
  
  RESULTS
  At surgery, 13 patients presented complete remission (CR), 32 partial remission (PR) and 20 no change of disease (NC). Pretherapeutic Her2/neu status was positively correlated with therapy response (p=0.019). DNA biomarkers before onset of therapy cycles 1, 2 and 6 did not indicate outcome after therapy. However, kinetics of ALU 115 from cycle 1 to 6 showed decreases in CR patients, while in NC patients, an increase was observed (p=0.033). Similar tendencies were found for ALU 247 fragments. DNA integrity index as well as CEA and CA 15-3 were not informative for therapy outcome.
  
  
  CONCLUSIONS
  Kinetics of plasma DNA (ALU 115) is associated with response to neoadjuvant chemotherapy in patients with locally confined breast cancer.
authors.affiliation: Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Lehner
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Stötzer
authors.forename: Debora
authors.initials: D
authors.lastname: Fersching
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
mesh_terms: D000328:Adult; D000368:Aged; D020087:Alu Elements; D054316:Biomarkers, Pharmacological / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D004247:DNA / Q000097:blood*; D005260:Female; D015870:Gene Expression; D006651:Histocytochemistry; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood / Q000235:genetics; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009691:Nucleic Acid Denaturation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000235:genetics; D012074:Remission Induction
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D004247:DNA; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: ALU 115; ALU 247; DNA integrity; Neoadjuvant chemotherapy; Plasma