Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer

Breast Cancer Res. 2018 Nov 20;20(1):141. doi: 10.1186/s13058-018-1067-y.


Background: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive.

Methods: We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized by progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation. CTCs were quantified with the Parsortix microfluidic device. Clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling were evaluated for each patient.

Results: Among 73 patients, we detected at least one CTC per 7.5 ml of blood in 34 (46%). Of these, 22 (65%) had single CTCs only, whereas 12 (35%) featured both single CTCs and CTC clusters. Treatment with the monoclonal antibody denosumab correlated with the absence of CTCs, both when considering all patients and when considering only those with bone metastasis. We also found that low red blood cell count was associated with the presence of CTCs, whereas high CA 15-3 tumor marker, high mean corpuscular volume, high white blood cell count and high mean platelet volume associated specifically with CTC clusters.

Conclusions: In addition to blood count correlatives to single and clustered CTCs, we found that denosumab treatment associates with most patients lacking CTCs from their peripheral circulation. Prospective studies will be needed to validate the involvement of denosumab in the prevention of CTC generation.

Keywords: Breast cancer; Circulating tumor cell clusters; Circulating tumor cells; Denosumab; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Count / methods
  • Denosumab / pharmacology*
  • Denosumab / therapeutic use
  • Disease Progression
  • Erythrocytes*
  • Female
  • Humans
  • Microfluidic Analytical Techniques / methods
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplastic Cells, Circulating / drug effects*
  • Prognosis
  • Retrospective Studies


  • Antineoplastic Agents
  • Denosumab