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Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis

Hartkopf, Andreas D. ; Brucker, Sara Y. ; Taran, Florin Andrei ; Harbeck, Nadia ; von Au, Alexandra ; Naume, Bjørn ; Pierga, Jean Yves ; Hoffmann, Oliver ; Beckmann, Matthias W. and Rydén, Lisa LU orcid , et al. (2021) In European Journal of Cancer 154. p.128-137
Abstract

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival... (More)

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Bone marrow, Disseminated tumour cells, Early breast cancer, Micrometastases, Prognosis, Tumour staging
in
European Journal of Cancer
volume
154
pages
10 pages
publisher
Elsevier
external identifiers
  • pmid:34265505
  • scopus:85109506986
ISSN
0959-8049
DOI
10.1016/j.ejca.2021.06.028
language
English
LU publication?
yes
id
62cfd7fb-e0b6-4b26-bfa8-eb45bf747e9b
date added to LUP
2021-08-16 13:44:16
date last changed
2024-07-13 16:50:57
@article{62cfd7fb-e0b6-4b26-bfa8-eb45bf747e9b,
  abstract     = {{<p>Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p &lt; 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p &lt; 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.</p>}},
  author       = {{Hartkopf, Andreas D. and Brucker, Sara Y. and Taran, Florin Andrei and Harbeck, Nadia and von Au, Alexandra and Naume, Bjørn and Pierga, Jean Yves and Hoffmann, Oliver and Beckmann, Matthias W. and Rydén, Lisa and Fehm, Tanja and Aft, Rebecca and Solà, Montserrat and Walter, Vincent and Rack, Brigitte and Schuetz, Florian and Borgen, Elin and Ta, Minh Hanh and Bittner, Ann Kathrin and Fasching, Peter A. and Fernö, Mårten and Krawczyk, Natalia and Weilbaecher, Katherine and Margelí, Mireia and Hahn, Markus and Jueckstock, Julia and Domschke, Christoph and Bidard, Francois Clement and Kasimir-Bauer, Sabine and Schoenfisch, Birgitt and Kurt, Ayse G. and Wallwiener, Markus and Gebauer, Gerhard and Klein, Christoph A. and Wallwiener, Diethelm and Janni, Wolfgang and Pantel, Klaus}},
  issn         = {{0959-8049}},
  keywords     = {{Bone marrow; Disseminated tumour cells; Early breast cancer; Micrometastases; Prognosis; Tumour staging}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{128--137}},
  publisher    = {{Elsevier}},
  series       = {{European Journal of Cancer}},
  title        = {{Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis}},
  url          = {{http://dx.doi.org/10.1016/j.ejca.2021.06.028}},
  doi          = {{10.1016/j.ejca.2021.06.028}},
  volume       = {{154}},
  year         = {{2021}},
}