Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): Prognosis, drug resistance and phenotypic characterization

A. Gradilone, G. Naso, C. Raimondi, E. Cortesi, O. Gandini, B. Vincenzi, R. Saltarelli, E. Chiapparino, F. Spremberg, M. Cristofanilli, L. Frati, A. M. Aglianò, P. Gazzaniga*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


Background: The expression of ATP-binding cassette transporters on circulating tumor cells (CTCs) is predictive of response to chemotherapy in cancer patients. We tested the hypothesis that drug-resistant CTCs might have predictive value in metastatic breast cancer (MBC) and possibly retain stem-like properties. Patients and methods: CTCs obtained from 42 MBC patients were evaluated for multidrug-resistance-related proteins (MRPs), aldehyde dehydrogenase 1 (ALDH1), estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2/neu). Primary objective was to evaluate the prognostic and predictive value of CTCs profile. Secondary end points were the level of concordance in ERα and HER2/neu status between primary tumors and CTCs and the correlation in CTCs between ALDH1, drug resistance profile and number of MRPs. Results: A difference in progression-free survival (PFS) was found between CTCs-positive and CTCs-negative patients. PFS was shorter in patients with a 'drug resistance' CTCs profile and in patients whose CTCs expressed two or more MRPs. No correlation was found between tumor characteristics and ALDH1. ALDH1 correlated to negative ERα and positive HER2/neu status in CTCs. The correlation between the number of MRPs expressed in CTCs and ALDH1 was statistically significant. Conclusion: In MBC, the presence of CTCs expressing MRPs and ALDH1 is predictive of response to chemotherapy.

Original languageEnglish (US)
Pages (from-to)86-92
Number of pages7
JournalAnnals of Oncology
Issue number1
StatePublished - Jan 2011


  • Breast cancer
  • Cancer stem cells
  • Circulating tumor cells
  • Drug resistance

ASJC Scopus subject areas

  • Hematology
  • Oncology


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