Circulating tumor cell clusters are frequently detected in women with early-stage breast cancer

Carolina Reduzzi, Serena Di Cosimo, Lorenzo Gerratana, Rosita Motta, Antonia Martinetti, Andrea Vingiani, Paolo D’amico, Youbin Zhang, Marta Vismara, Catherine Depretto, Gianfranco Scaperrotta, Secondo Folli, Giancarlo Pruneri, Massimo Cristofanilli, Maria Grazia Daidone, Vera Cappelletti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The clinical relevance of circulating tumor cell clusters (CTC-clusters) in breast cancer (BC) has been mostly studied using the CellSearch®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, and ScreenCell® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch® (median number = 7 versus 1, p = 0.0038). Next, samples from 37 early BC (EBC) and 23 metastatic BC (MBC) patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification (based on cytomorphological criteria). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients (median number = 2, range 0–20, versus 0, range 0–15, p = 0.0015). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history.

Original languageEnglish (US)
Article number2356
Issue number10
StatePublished - May 2 2021


  • Circulating tumor cell clusters
  • Circulating tumor microemboli
  • Early breast cancer
  • Liquid biopsy
  • Metastatic breast cancer
  • Size-based enrichment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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