title: Significance of Circulating Tumor Cells in Metastatic Triple-Negative Breast Cancer Patients within a Randomized, Phase II Trial: TBCRC 019.
abstract: OBJECTIVE
  Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). We tested whether EpCAM-based capture system (CellSearch) is effective in patients with triple-negative (TN) MBC, and whether CTC apoptosis and clustering enhances the prognostic role of CTC.
  
  
  METHODS
  CTC enumeration and apoptosis were determined using the CXC CellSearch kit at baseline and days 15 and 29 in blood drawn from TN MBC patients who participated in a prospective randomized phase II trial of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without tigatuzumab. Association between levels of CTC and patient outcomes was assessed using logistic regression, Kaplan-Meier curves, and Cox proportional hazards modeling.
  
  
  RESULTS
  Nineteen of 52 (36.5%), 14 of 52 (26.9%), and 13 of 49 (26.5%) patients who were evaluable had elevated CTC (≥5 CTC/7.5 mL whole blood) at baseline and at days 15 and 29, respectively. Patients with elevated versus not elevated CTC at each time point had worse progression-free survival (PFS; P = 0.005, 0.0003, 0.0002, respectively). The odds of clinical benefit response for those who had elevated versus low CTC at baseline and days 15 and 29 were 0.25 (95% CI: 0.08-0.84; P = 0.024), 0.19 (95% CI: 0.05-0.17; P = 0.014), and 0.06 (95% CI: 0.01-0.33; P = 0.001), respectively. There was no apparent prognostic effect comparing CTC apoptosis versus non-apoptosis. Presence of CTC cluster at day 15 and day 29 was associated with shorter PFS.
  
  
  CONCLUSIONS
  CTC were detected using CellSearch assay in approximately one-third of TN MBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic, and reductions in CTC levels reflected response.
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Costanza
authors.initials: C
authors.lastname: Paoletti
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Muñiz
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan. Univeristy of Michigan, Department of Biostatistics, Ann Arbor, Michigan.
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Kidwell
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Aung
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Brown
authors.affiliation: Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
authors.forename: Vandana G
authors.initials: VG
authors.lastname: Abramson
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina. Bon Secours Cancer Institute, Midlothian, Virginia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Irvin
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
authors.affiliation: Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Minetta C
authors.initials: MC
authors.lastname: Liu
authors.affiliation: University of Chicago, Chicago, Illinois.
authors.forename: Rita
authors.initials: R
authors.lastname: Nanda
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Nangia
authors.affiliation: Indiana University Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Storniolo
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Traina
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Christos
authors.initials: C
authors.lastname: Vaklavas
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Van Poznak
authors.affiliation: Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
authors.affiliation: Comprehensive Cancer Center and the Department of Internal Medicine, University of Michigan Health and Hospital System, Ann Arbor, Michigan. hayesdf@umich.edu.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002452:Cell Count; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C552861:tigatuzumab; D017239:Paclitaxel