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

Marcus Vetter,Alexandra Malinovska,Sofia Gkountela,Christian Kurzeder,Barbara Maria Szczerba,Alfred Zippelius,Ilona Krol,Ramona Scherrer,Nicola Aceto,Catharina Balmelli,Christoph Rochlitz,Viola Heinzelmann-Schwarz,Francesc Castro-Giner,Julia Landin,Walter Paul Weber,Cinzia Donato

doi:10.1186/s13058-018-1067-y

Abstract

BackgroundThe 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.MethodsWe 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.ResultsAmong 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.ConclusionsIn 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.

Highlights

The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis
We aimed to investigate a number of clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling in a cohort of 73 consecutive patients with invasive breast cancer characterized by progressive disease, high tumor load and treatment discontinuation at the time of CTC isolation, before the line of therapy
Patient characteristics Given previously reported correlations between number of CTCs and tumor load [8], as well as the findings that CTC counts predict poor prognosis in breast cancer [3, 4, 9], we focused on a group of 73 consecutive patients with invasive breast cancer with the following characteristics: high tumor load, detailed treatment history available, progressive disease associated with treatment discontinuation at the time of CTC isolation, and availability of comprehensive blood counts performed at CTC collection

Summary

Introduction

The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive. We aimed to investigate a number of clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling in a cohort of 73 consecutive patients with invasive breast cancer characterized by progressive disease, high tumor load and treatment discontinuation (or without any pretreatment) at the time of CTC isolation, before the line of therapy. The rationale of our study was to identify, in an unbiased manner (i.e., not driven by preexisting hypotheses), clinical parameters that correlate with CTC presence in patients with progressive breast cancer

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