Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Breast Cancer Res Treat. 2009 Oct;117(3):525-34. doi: 10.1007/s10549-008-0239-3. Epub 2008 Nov 19.


To evaluate whether HER2 mRNA could be used as a marker of circulating tumor cells (CTCs) in women with operable breast cancer. A nested RT-PCR assay was developed and used for the detection of HER2 mRNA-positive CTCs. Blood from 216 women with early breast cancer obtained before adjuvant treatment was tested for HER2 mRNA-positive cells to assess their prognostic value. Nested RT-PCR for HER2 mRNA showed high sensitivity whereas no HER2 mRNA-positive cells could be identified in the blood of healthy donors. HER2 mRNA-positive CTCs were detected in 53 (24.5%) of 216 patients and HER2 mRNA detection was associated with reduced disease-free survival (DFS; P < 0.0001) and overall survival (OS; P = 0.004). In multivariate analysis, detection of HER2 mRNA-positive CTCs emerged as independent prognostic factor for DFS (P = 0.0001) and OS (P = 0.003). HER2 mRNA could be a valuable prognostic marker for the detection of CTCs in early breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / blood*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Microscopy, Confocal
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • RNA, Messenger / analysis*
  • RNA, Messenger / blood
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptor, ErbB-2