title: Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial.
abstract: OBJECTIVE
  Circulating tumor cells in blood from metastatic breast cancer patients have been reported as a surrogate marker for tumor response and shorter survival. The aim of this study was to determine whether circulating tumor cells are present in the blood of patients with large operable or locally advanced breast cancer before neoadjuvant chemotherapy and after neoadjuvant chemotherapy before surgery.
  
  
  METHODS
  Blood samples of 7.5 mL were obtained on CellSave tubes from patients included in a phase II trial (REMAGUS 02). Circulating tumor cells were immunomagnetically separated and fluorescently stained by the CellSearch system. Blood from 20 metastatic breast cancer patients was used as a positive control.
  
  
  RESULTS
  From October 2004 to July 2006, preneoadjuvant chemotherapy and/or postneoadjuvant chemotherapy blood samples were obtained from 118 patients. At least 1 circulating tumor cell was detected in 22 of 97 patients with preneoadjuvant chemotherapy samples (23%; 95% confidence interval, 15-31%; median, 2 cells; range, 1-17 cells). Circulating tumor cell positivity rates were 17% in 86 postneoadjuvant chemotherapy samples and 27% in all 118 patients. Persistence of circulating tumor cells at the end of neoadjuvant chemotherapy was not correlated with treatment response. After a short median follow-up of 18 months, the presence of circulating tumor cells (P=0.017), hormone receptor negativity, and large tumor size were independent prognostic factors for shorter distant metastasis-free survival.
  
  
  CONCLUSIONS
  Circulating tumor cells can be detected by the CellSearch system at a low cutoff of 1 cell in 27% of patients receiving neoadjuvant chemotherapy. Circulating tumor cell detection was not correlated to the primary tumor response but is an independent prognostic factor for early relapse.
authors.affiliation: Institut Curie, Paris, France. jean-yves.pierga@curie.net
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: François-Clément
authors.initials: FC
authors.lastname: Bidard
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giachetti
authors.forename: Patricia
authors.initials: P
authors.lastname: de Cremoux
authors.forename: Rémy
authors.initials: R
authors.lastname: Salmon
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Michel
authors.initials: M
authors.lastname: Marty
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents