Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer

Ann Oncol. 2007 Oct;18(10):1623-31. doi: 10.1093/annonc/mdm208. Epub 2007 May 21.


Background: The purpose of this study was to evaluate the effect of adjuvant treatment with tamoxifen on the CK-19 mRNA+ cells in patients with early-stage breast cancer.

Patients and methods: CK-19 mRNA+ cells were prospectively and longitudinally detected using a specific real-time PCR assay for CK-19 mRNA in 119 patients with estrogen and/or progesterone receptor-positive tumors during the period of tamoxifen administration.

Results: Twenty-two (18.5%) patients had detectable CK-19 mRNA+ cells after the completion of adjuvant chemotherapy and in 15 (68.2%) of them adjuvant tamoxifen could not eliminate these cells (persistently positive). In 68 (57.1%) patients, no CK-19 mRNA+ cells could be detected throughout the follow-up period (persistently negative). Seven (46.7%) of the 15 persistently positive and six (8.8%) of the 68 persistently negative patients developed disease recurrence (P = 0.00026). Persistency of CK-19 mRNA+ cells was associated with a significantly lower median disease-free interval (P = 0.0001) and overall survival (P = 0.0005). Multivariate analysis revealed that the detection of CK-19 mRNA+ cells during the administration of tamoxifen was associated with an increased risk of relapse [hazard ratio (HR) = 22.318, P = 0.00006] and death (HR = 13.954, P < 0.00001).

Conclusions: The detection of CK-19 mRNA+ cells throughout the period of adjuvant tamoxifen treatment is an independent poor prognostic factor in patients with early breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Chemotherapy, Adjuvant
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Humans
  • Keratin-19 / genetics*
  • Longitudinal Studies
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplastic Cells, Circulating*
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / blood*
  • Tamoxifen / therapeutic use*


  • Estrogen Antagonists
  • Keratin-19
  • RNA, Messenger
  • Tamoxifen