TY - JOUR
T1 - Disseminated tumour cells from the bone marrow of early breast cancer patients
T2 - Results from an international pooled analysis
AU - Hartkopf, Andreas D.
AU - Brucker, Sara Y.
AU - Taran, Florin Andrei
AU - Harbeck, Nadia
AU - von Au, Alexandra
AU - Naume, Bjørn
AU - Pierga, Jean Yves
AU - Hoffmann, Oliver
AU - Beckmann, Matthias W.
AU - Rydén, Lisa
AU - Fehm, Tanja
AU - Aft, Rebecca
AU - Solà, Montserrat
AU - Walter, Vincent
AU - Rack, Brigitte
AU - Schuetz, Florian
AU - Borgen, Elin
AU - Ta, Minh Hanh
AU - Bittner, Ann Kathrin
AU - Fasching, Peter A.
AU - Fernö, Mårten
AU - Krawczyk, Natalia
AU - Weilbaecher, Katherine
AU - Margelí, Mireia
AU - Hahn, Markus
AU - Jueckstock, Julia
AU - Domschke, Christoph
AU - Bidard, Francois Clement
AU - Kasimir-Bauer, Sabine
AU - Schoenfisch, Birgitt
AU - Kurt, Ayse G.
AU - Wallwiener, Markus
AU - Gebauer, Gerhard
AU - Klein, Christoph A.
AU - Wallwiener, Diethelm
AU - Janni, Wolfgang
AU - Pantel, Klaus
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ADH, FAT and SYB report a grant from Exact Sciences. TNF received personal fees from AstraZeneca, Novartis, Roche, Pfizer, Esai, Tesaro, Teva, Celgene, Daichi Sankyo, MSD, Menarini. PAF reports grants from Cepheid, Novartis and Biontech, personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, Macrogenics, Eisai, Puma and Lilly. CAK is a member of the SAB of HiberCell, New York. All other authors declare no potential conflicts of interest.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Bone marrow
KW - Disseminated tumour cells
KW - Early breast cancer
KW - Micrometastases
KW - Prognosis
KW - Tumour staging
UR - http://www.scopus.com/inward/record.url?scp=85109506986&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.06.028
DO - 10.1016/j.ejca.2021.06.028
M3 - Article
C2 - 34265505
AN - SCOPUS:85109506986
SN - 0959-8049
VL - 154
SP - 128
EP - 137
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -