title: Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer.
abstract: BACKGROUND
  Enumeration of circulating tumor cells (CTC) from whole blood permits monitoring of patients with breast carcinoma. Analysis of apoptosis & Bcl-2 expression in CTC might add additional prognostic and predictive information. We estimated the degree of these markers in CTC from patients being treated for metastatic breast cancer.
  
  
  METHODS
  Eighty-three evaluable patients initiating a new therapy for metastatic breast cancer were enrolled. Whole blood was collected at baseline, at one of three short term time windows (24, 48, or 72 h) after initiating treatment, and at first follow-up (3-5 weeks). CTC were isolated, enumerated, and expression of M30 and Bcl2 was determined using the CellSearch(®) System.
  
  
  RESULTS
  At baseline, window, and 3-5 weeks post-treatment, 41/80 (51%), 40/80 (50%) and 21/75 (28%) patients had ≥5 CTC, respectively. At baseline, the proportion of CTC-apoptosis (M30) was inversely correlated with CTC number, and modestly inversely correlated with CTC-Bcl-2. As expected, higher CTC levels at baseline or first follow-up were associated with worse prognosis. Surprisingly, in patients with elevated CTC, higher levels of CTC-apoptosis were associated with worse prognosis, while higher CTC-Bcl-2 levels correlated with better outcomes.
  
  
  CONCLUSIONS
  CTC apoptosis and expression of Bcl-2 can be analytically determined in patients with metastatic breast cancer and may have biological and clinical implications. Characterization of CTC for these and other markers could further increase the utility of CTC monitoring patients in clinical investigations of new anti-neoplastic agents.
authors.affiliation: Breast Oncology Program of the Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, MI 48109, USA. smerage@med.umich.edu
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Smerage
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Doyle
authors.forename: Marty
authors.initials: M
authors.lastname: Brown
authors.forename: Costanza
authors.initials: C
authors.lastname: Paoletti
authors.forename: Maria
authors.initials: M
authors.lastname: Muniz
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Madeline I
authors.initials: MI
authors.lastname: Repollet
authors.forename: David A
authors.initials: DA
authors.lastname: Chianese
authors.forename: Mark C
authors.initials: MC
authors.lastname: Connelly
authors.forename: Leon W W M
authors.initials: LW
authors.lastname: Terstappen
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001940:Breast / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D002452:Cell Count; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010865:Pilot Projects; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2
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