title: Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes.
abstract: OBJECTIVE
  Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status.
  
  
  METHODS
  Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normal healthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status.
  
  
  RESULTS
  CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and >or=2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P<0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P=0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P=0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases.
  
  
  CONCLUSIONS
  The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California 90404, USA.
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Steve R
authors.initials: SR
authors.lastname: Martinez
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Goto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koyanagi
authors.forename: Minoru
authors.initials: M
authors.lastname: Kitago
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shingai
authors.forename: David A
authors.initials: DA
authors.lastname: Elashoff
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Singer
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D021701:Sentinel Lymph Node Biopsy
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone