Differential effect of adjuvant taxane-based and taxane-free chemotherapy regimens on the CK-19 mRNA-positive circulating tumour cells in patients with early breast cancer

Br J Cancer. 2013 Feb 19;108(3):549-56. doi: 10.1038/bjc.2012.597. Epub 2013 Jan 17.

Abstract

Background: To determine the effect of adjuvant taxane-free and taxane-based chemotherapy regimens on the elimination of circulating tumour cells (CTCs) in patients with early breast cancer.

Methods: The presence of CK-19 mRNA-positive CTCs in the peripheral blood was evaluated before and after chemotherapy, using a real-time RT-PCR assay, in a historical comparison of two cohorts of women with stage I-III breast cancer treated with adjuvant taxane-free (N=211; FE(75)C or E(75)C) and taxane-based (N=334; T/E(75)C or T/E(75)) chemotherapy.

Results: Taxane-based chemotherapy resulted in a higher incidence of CTCs' elimination than taxane-free regimens since 49.7% (74 of 149) and 33.0% (29 of 88) of patients with detectable CTCs before chemotherapy, respectively, turned negative post-chemotherapy (P=0.015). Patients treated with taxane-free regimens had a significantly lower disease-free survival (DFS) (P=0.035) than patients treated with taxane-based regimens; this difference was observed in patients with but not without detectable CTCs before chemotherapy (P=0.018 and P=0.481, respectively). The incidence of deaths was significantly higher in the taxane-free cohort of patients with but not without detectable CTCs before chemotherapy compared with that of the taxane-based cohort (P=0.002). Multivariate analysis revealed that the chemotherapy regimen was significantly associated with prolonged DFS (HR: 2.00; 95% CI=1.20-3.34).

Conclusion: Elimination of CK-19 mRNA-positive CTCs during adjuvant chemotherapy seems to be an efficacy indicator of treatment and is associated with a favourable clinical outcome of patients with detectable CTCs before chemotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Chemotherapy, Adjuvant
  • Docetaxel
  • Female
  • Follow-Up Studies
  • Humans
  • Keratin-19 / blood
  • Keratin-19 / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / pathology*
  • Paclitaxel / administration & dosage
  • Prognosis
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Taxoids / administration & dosage

Substances

  • Keratin-19
  • RNA, Messenger
  • Taxoids
  • Docetaxel
  • Receptor, ErbB-2
  • Paclitaxel