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

• Published in: Breast cancer research : BCR Vol. 20; no. 1; p. 141
• Main Authors: Vetter, Marcus, Landin, Julia, Szczerba, Barbara Maria, Castro-Giner, Francesc, Gkountela, Sofia, Donato, Cinzia, Krol, Ilona, Scherrer, Ramona, Balmelli, Catharina, Malinovska, Alexandra, Zippelius, Alfred, Kurzeder, Christian, Heinzelmann-Schwarz, Viola, Weber, Walter Paul, Rochlitz, Christoph, Aceto, Nicola
• Format: Journal Article
• Language: English
• Published: England BioMed Central 20-11-2018; BMC
• Subjects: Blood; Breast cancer; Cell adhesion & migration; Circulating tumor cell clusters; Circulating tumor cells; Denosumab; Enumeration; Epidermal growth factor; Erythrocytes; Immunotherapy; Invasiveness; Medical prognosis; Metastases; Metastasis; Microfluidics; Monoclonal antibodies; Patients; Studies; Targeted cancer therapy; Tumor cells; Tumor markers; United States > US; Breast cancer; Circulating tumor cells; Metastasis; Denosumab; Circulating tumor cell clusters
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-018-1067-y

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.
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.
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.
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.