title: Detection of minimal residual disease in blood and bone marrow in early stage breast cancer.
abstract: BACKGROUND
  The significance of circulating tumor cells (CTCs) in blood and of disseminated tumor cells (DTCs) in bone marrow (BM) in patients with early stage breast cancer is unclear. In this study, the authors investigated the occurrence of CTCs and DTCs in women with early stage breast cancer and evaluated the correlation of their presence with other prognostic markers.
  
  
  METHODS
  Blood and BM aspirations were collected at the time of primary breast surgery. CTCs were detected by using the CellSearch assay, and DTCs were detected by immunostaining BM aspirates for pancytokeratin. The presence of CTCs and DTCs was correlated with tumor classification (T1 vs T2), tumor histologic grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and lymph node (LN) status.
  
  
  RESULTS
  Of 92 patients who were included in the study, 49 had T1 tumors, and 43 had T2 tumors. CTCs were detected in 31% of patients, and DTCs were detected in 27% of patients. There was no correlation between the occurrence of CTCs and DTCs with the tumor classification (T1 vs T2) or histologic grade. CTCs were detected in 33% of patients with ER-positive disease versus 26% of patients with ER-negative disease, in 32% of patients with PR-positive disease versus 30% of patients with PR-negative disease, and in 25% of patients with HER2-positive disease versus 31% of patients with HER2-negative disease. DTCs were observed in 23% of patients with ER-positive disease versus 37% of patients with ER-negative disease, in 22% of patients with PR-positive disease versus 32% of patients with PR-negative disease, and in 0% of patients with HER2-positive disease versus 29% of patients with HER2-negative disease. CTCs and DTCs were nearly equally prevalent in both LN-positive women and LN-negative women. There was no significant correlation between the occurrence of CTCs or DTCs with tumor classification (T1 vs T2), tumor histologic grade, positive ER status, positive PR status, or positive HER2 status, and axillary LN status.
  
  
  CONCLUSIONS
  CTCs and DTCs in women with early stage breast cancer did not correlate with the standard prognostic indicators that were considered. The implications of their occurrence in patients with early stage disease will require further large-scale studies.
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Balraj
authors.initials: B
authors.lastname: Singh
authors.forename: James
authors.initials: J
authors.lastname: Reuben
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: Eleni
authors.initials: E
authors.lastname: Andreopoulou
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Hall
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Lodhi
authors.forename: Summer
authors.initials: S
authors.lastname: Jackson
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018365:Neoplasm, Residual / Q000097:blood / Q000473:pathology*; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D011379:Prognosis