Evidence map›Paper›PMID 31992773›Full record

Trial reportScientific reports2020

Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer.

Francesco Pantano, Elisabetta Rossi, Michele Iuliani, Antonella Facchinetti, Sonia Simonetti, Giulia Ribelli, Alice Zoccoli, Bruno Vincenzi, Giuseppe Tonini, Rita Zamarchi and 1 more

Abstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Francesco Pantano *Medical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.
Elisabetta Rossi *Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0002-5242-9568
Michele IulianiMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy. m.iuliani@unicampus.it.ORCID http://orcid.org/0000-0003-3536-7630
Antonella FacchinettiDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0002-5628-5899
Sonia SimonettiMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.
Giulia RibelliMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.
Alice ZoccoliMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0003-1991-1667
Bruno VincenziMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.
Giuseppe ToniniMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.
Rita ZamarchiVeneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Daniele SantiniMedical Oncology Department of Campus Bio-Medico, University of Rome, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor-activator of nuclear-factor -κB-ligand (RANKL) and its receptor RANK have been recently identified as key players in breast cancer bone metastases. Since Circulating Tumor Cells (CTCs) are considered a crucial step of metastatic process, we explored RANK expression on CTCs in metastatic breast cancer (MBC), and the predictive value of RANK-positive CTCs in monitoring patients during treatment with denosumab (anti-RANKL antibody). To this purpose, we developed a novel CTC assay to quantify RANK-positive CTCs in forty-two bone MBC patients, candidates to denosumab treatment. Companion algorithms ΔAUC and Slope were developed, and correlated with time to first skeletal-related-events (SRE), time to bone metastasis progression and time to visceral metastasis progression. Twenty-seven patients had at least one CTC at baseline and, among these, nineteen (70%) had one or more RANK-positive CTCs. Notably, the baseline total CTCs, but not the RANK-positive, were associated with Time-to-first-SRE, Time-to-Bone-Metastasis-Progression and Time-to-Visceral-Metastasis-Progression. Conversely, during treatment monitoring, positive ΔAUC value, expression of RANK-positive CTCs persistence, correlated with longer Time-to-first-SRE (p = 0.0002) and Time-to-Bone-Metastasis-Progression (p = 0.0012). Furthermore, the early increase at second day, in RANK-positive CTCs (Positive-Slope) was associated with delay in time-to-first-SRE (p = 0.0038) and Time-to-Bone-Metastasis-Progression (p = 0.0024). We demonstrate, for the first time, the expression of RANK on CTCs in MBC patients and that the persistence of RANK expression determines denosumab effectiveness.

Indexed as

Breast NeoplasmsAdultAgedAged, 80 and overDenosumabFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm MetastasisNeoplasm ProteinsNeoplastic Cells, CirculatingPilot ProjectsRANK LigandDenosumabNeoplasm ProteinsRANK LigandTNFSF11 protein, human

Identifiers

PMID31992773
PMCPMC6987166

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.