Evidence map›Paper›PMID 27390845›Full record

Observational studyBMC cancer2016

Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort.

Sara Jansson, Pär-Ola Bendahl, Anna-Maria Larsson, Kristina E Aaltonen, Lisa Rydén

Registry-linked trialOpen access · goldAbstract readObservational Study
In one paragraph

Observational study in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322893 (Enumeration and Molecular Characterization of Circulating Tumour Cells in Women With Metastatic Breast Cancer), which is not on this map. Cited by 109 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 2 pooled it
7.4field-weighted citation impact, top 2% of its field
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.

NCT01322893 completednot on this map

Enumeration and Molecular Characterization of Circulating Tumour Cells in Women With Metastatic Breast Cancer

TypeobservationalSponsorLund University HospitalRan2011 to 2016Enrolled150ConditionsMetastatic Breast Cancer
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 166 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. A Novel Workflow to Enrich and Isolate Patient-Matched EpCAMInternational journal of molecular sciences · 2017
    Trial
  5. Review
  6. Article
  7. Article
  8. Circulating Tumor Cells: Emerging Frontiers in Cancer Technology.Expert reviews in molecular medicine · 2026
    Review
  9. Article
  10. Role of circulating tumor cell clusters in breast cancer.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Personalized treatment approach for HER2-positive metastatic breast cancer.Medical oncology (Northwood, London, England) · 2024
    Review
  20. Article

49 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Sara JanssonDivision of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE-223 81, Lund, Sweden.
Pär-Ola BendahlDivision of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE-223 81, Lund, Sweden.
Anna-Maria LarssonDivision of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE-223 81, Lund, Sweden.
Kristina E AaltonenDivision of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE-223 81, Lund, Sweden.
Lisa RydénDepartment of Surgery, Skåne University Hospital, SE-214 28, Malmö, Sweden. lisa.ryden@med.lu.se.
Lund University · SESkåne University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPresence of circulating tumor cells (CTCs) is a validated prognostic marker in metastatic breast cancer. Additional prognostic information may be obtained by morphologic characterization of CTCs. We explored whether apoptotic CTCs, CTC clusters and leukocytes attached to CTCs are associated with breast cancer subtype and prognosis at base-line (BL) and in follow-up (FU) blood samples in patients with metastatic breast cancer scheduled for first-line systemic treatment.

methodsPatients with a first metastatic breast cancer event were enrolled in a prospective observational study prior to therapy initiation and the CellSearch system (Janssen Diagnostics) was used for CTC enumeration and characterization. We enrolled patients (N = 52) with ≥5 CTC/7.5 ml blood at BL (median 45, range 5-668) and followed them with blood sampling for 6 months during therapy. CTCs were evaluated for apoptotic changes, CTC clusters (≥3 nuclei), and leukocytes associated with CTC (WBC-CTC, ≥1 CTC + ≥1 leukocytes) at all time-points by visual examination of the galleries generated by the CellTracks Analyzer.

resultsAt BL, patients with triple-negative and HER2-positive breast cancer had blood CTC clusters present more frequently than patients with hormone receptor-positive cancer (P = 0.010). No morphologic characteristics were associated with prognosis at BL, whereas patients with apoptotic CTCs or clusters in FU samples had worse prognosis compared to patients without these characteristics with respect to progression-free (PFS) and overall survival (OS) (log-rank test: P = 0.0012 or lower). Patients with apoptotic or clustered CTCs at any time-point had impaired prognosis in multivariable analyses adjusting for number of CTCs and other prognostic factors (apoptosis: HROS = 25, P < 0.001; cluster: HROS = 7.0, P = 0.006). The presence of WBC-CTCs was significantly associated with an inferior prognosis in terms of OS at 6 months in multivariable analysis.

conclusionsPatients with a continuous presence of apoptotic or clustered CTCs in FU samples after systemic therapy initiation had worse prognosis than patients without these CTC characteristics. In patients with ≥5 CTC/7.5 ml blood at BL, morphologic characterization of persistent CTCs could be an important prognostic marker during treatment, in addition to CTC enumeration alone. Clinical Trials (NCT01322893), registration date 21 March 2011.

Indexed as

ApoptosisAdultAgedAged, 80 and overBreast NeoplasmsDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMiddle AgedMultivariate AnalysisNeoplastic Cells, CirculatingPrognosisProportional Hazards ModelsProspective StudiesApoptosisCirculating tumor cellsClustersMetastatic breast cancerMorphology

Identifiers

PMID27390845
PMCPMC4938919
OpenAlexW2460702286

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.