title: Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients.
abstract: BACKGROUND
  To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C), and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC).
  
  
  METHODS
  CTCBL and CTC1C status was determined as negative (-) or positive (+) for < 5 or ≥ 5 CTCs/7.5 ml blood using CellSearch™ (Veridex). CTCKIN was categorized as favorable (CTC1C-) or unfavorable (CTC1C+). Tumor response was to be assessed every 2-3 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Statistical analysis focused on the relation between CTC status and CTCKIN, and response, PFS, and OS.
  
  
  RESULTS
  133/393 (34%) patients enrolled were CTCBL+. CTC1C status after one cycle and radiological tumor response were assessed after median (range) periods of 1.2 (0.5-3.2) and 2.9 (0.5-4.8) months, respectively. 57/201 (28%) were CTC1C+. Median [95% confidence interval] PFS and OS (months) were significantly reduced in CTCBL+ vs. CTCBL- patients (PFS 4.7 [3.7-6.1] vs. 7.8 [6.4-9.2]; OS 10.4 [7.9-15.0] vs. 27.2 [22.3-29.9]), and for CTC1C+ vs. CTC1C- patients (PFS 4.3 [3.6-6.0] vs. 8.5 [6.6-10.4]; OS 7.7 [6.4-13.9] vs. 30.6 [22.6-not available]). Unfavorable CTCKIN was significantly associated with progressive disease. Multivariate Cox regression analysis revealed prognostic factors for shorter PFS (CTCBL+, persistent CTCs after one cycle, ≥ 3rd-line therapy, and triple-negative receptor status) and shorter OS (CTCBL+, persistent CTCs after one cycle, bone-and-visceral/local metastases, ≥ 3rd-line therapy, and triple-negative receptor status).
  
  
  CONCLUSIONS
  CTCBL, CTC1C, and CTCKIN are predictive of outcome in MBC. Serial CTC enumeration is useful in tailoring systemic treatment of MBC.
  
  
  BACKGROUND
  Not applicable.
authors.affiliation: National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. markus.wallwiener@med.uni-heidelberg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Andreas Daniel
authors.initials: AD
authors.lastname: Hartkopf
authors.forename: Caroline
authors.initials: C
authors.lastname: Modugno
authors.forename: Juliane
authors.initials: J
authors.lastname: Nees
authors.forename: Dharanija
authors.initials: D
authors.lastname: Madhavan
authors.forename: Martin Ronald
authors.initials: MR
authors.lastname: Sprick
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.forename: Christoph
authors.initials: C
authors.lastname: Domschke
authors.forename: Irène
authors.initials: I
authors.lastname: Baccelli
authors.forename: Birgitt
authors.initials: B
authors.lastname: Schönfisch
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Jörg
authors.initials: J
authors.lastname: Heil
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor