title: Circulating tumor cells as predictors of response and failure in breast cancer patients treated with preoperative chemotherapy.
abstract: OBJECTIVE
  To explore the significance of circulating tumor cells (CTCs) detection in the course of preoperative chemotherapy (PC) and their effect on the outcomes.
  
  
  METHODS
  Fifty-five patients with stage II/III invasive breast cancer were enrolled into a preoperative clinical trial. Patients were given PC with sequential single-agent doxorubicin and paclitaxel vs paclitaxel followed by doxorubicin. Blood samples (8 mL) were collected from patients before PC, after each phase, and at 6 months intervals during follow-up. Peripheral blood mononuclear cells were isolated and enriched for epithelial cells. Quantitative RT-PCR was used to determine the presence of cytokeratin 19 (CK19) mRNA. Samples were considered positive when the PCR curve crossed the standard threshold curve.
  
  
  RESULTS
  After the first phase of chemotherapy, there was a 59% overall reduction in the median tumor volume. The percentage of volume reduction did not differ between patients who presented with detectable CTCs at baseline and those who did not (p=0.89). After the second phase of chemotherapy, there was a further decrease in the median tumor volume to 93% from baseline. There was no correlation between the lack of response and the presence of CTCs either after the first (p=0.36) or second (p=0.5391) phases of PC. The presence of CTCs was a predictor of local or distant relapse (p=0.0411). The detection of CTCs did not affect overall survival (p=0.2569).
  
  
  CONCLUSIONS
  CTCs can be used as predictors of relapse after definitive treatment of locally advanced breast cancer; however, CTCs detection in peripheral blood during the course of PC does not implicate a particular pattern of response to treatment.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Rimoun R
authors.initials: RR
authors.lastname: Boutrus
authors.forename: Rita F
authors.initials: RF
authors.lastname: Abi Raad
authors.forename: Irene
authors.initials: I
authors.lastname: Kuter
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: Lisa
authors.initials: L
authors.lastname: Roberts
authors.forename: Natalie
authors.initials: N
authors.lastname: Solomon
authors.forename: Taylor
authors.initials: T
authors.lastname: Ngo
authors.forename: Heather
authors.initials: H
authors.lastname: Borick
authors.forename: Paula
authors.initials: P
authors.lastname: Ryan
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.forename: Michele
authors.initials: M
authors.lastname: Gadd
authors.forename: Jo
authors.initials: J
authors.lastname: Chien
authors.forename: Jerry
authors.initials: J
authors.lastname: Younger
authors.forename: Barbara
authors.initials: B
authors.lastname: Smith
authors.forename: Alphonse G
authors.initials: AG
authors.lastname: Taghian
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008408:Mastectomy; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19