title: Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination.
abstract: BACKGROUND
  Traditional factors currently used for prognostic stratification do not always adequately predict treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.
  
  
  METHODS
  A total of 492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 CTCs/7.5 ml of blood, pretreatment CTC counts were correlated in the overall population with metastatic site distribution, evaluated at baseline and at the time of treatment failure, using Fisher's exact test. Time to visceral progression and time to the development of new metastatic lesions and sites were estimated in patients with nonvisceral metastases and with single-site metastatic disease, respectively, by the Kaplan-Meier method. Survival times were compared between groups according to pretreatment CTC count by logrank test.
  
  
  RESULTS
  In the overall population, a pretreatment level ≥5 CTCs/7.5 ml was associated with an increased baseline number of metastatic sites compared with <5 CTCs/7.5 ml (P = 0.0077). At the time of treatment failure, patients with ≥5 CTCs/7.5 ml more frequently developed new metastatic lesions and sites compared with those with <5 CTCs/7.5 ml (development of new lesions: P = 0.0002; development of new sites: P = 0.0031). Among patients with disease originally confined to nonvisceral sites, ≥5 CTCs/7.5 ml was associated with remarkably shorter time to visceral metastases (P = 0.0021) and overall survival (P = 0.0006) compared with <5 CTCs/7.5 ml. In patients with single-site metastatic disease, ≥5 CTCs/7.5 ml was associated with a significant reduction of the time to development of new metastatic sites (P = 0.0051) and new lesions (P = 0.0002) and with worse overall survival (P = 0.0101).
  
  
  CONCLUSIONS
  Our results suggest that baseline CTC counts can be used as an early predictor of metastatic potential in breast cancer patients with limited metastatic dissemination.
authors.forename: Mario
authors.initials: M
authors.lastname: Giuliano
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Summer
authors.initials: S
authors.lastname: Jackson
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Simone
authors.initials: S
authors.lastname: Anfossi
authors.forename: Beverly C
authors.initials: BC
authors.lastname: Handy
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Alvarez
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D001859:Bone Neoplasms / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models