Abstract GS5-07: International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study
Authors: Hartkopf AD , Brucker SY , Taran F-A , Harbeck N , von Au A , Naume B , Pierga J-Y , Hoffmann O , Beckmann MW , Rydén L , Fehm T , Aft R , Montserrat S , Walter V , Rack B , Schuetz F , Borgen E , Ta M-H , Bittner A-K , Fasching P , Fernö M , Krawczyk N , Weilbaecher K , Margelí M , Hahn M , Jueckstock J , Domschke C , Bidard F-C , Kasimir-Bauer S , Schoenfisch B , Kurt AG , Wallwiener M , Gebauer G , Wallwiener D , Janni W , Pantel K 
Published: May 2019

Abstract
Introduction
As early breast cancer might relapse even after complete removal of breast and lymphnodes, the disease must persist in secondary sites. The detection of disseminated tumor cells (DTC) in the bone marrow (BM) has been described as a surrogate of residual disease. Various trials showed an impaired prognosis of DTC positive early breast cancer (EBC) patients. The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is a large international pooled analysis that aimed to assess the prognostic impact of DTC detection in patients with EBC.
Methods
A pre-specified protocol was followed, and centers known to practice BM sampling for DTC detection were contacted for individual patient data. Patients with EBC, with available follow-up data and BM sampling before any anti-cancer treatment were eligible. BM aspirates were collected at the time of primary surgery. DTC were identified by antibody (A45-B/B3, AE1/AE3, 2E11 and E29) staining against cytokeratin. The DTC status was compared to other prognostic factors using the chi-squared test. Univariate log-rank test and multivariate cox regression were used to compare survival of DTC positive versus DTC negative patients.
Results
Individual data from 10,320 patients (11 centers from Europe and USA) were included with a median follow-up of 91 months. Of all patients, 2,823 (27.4 %) were DTC positive. DTC detection was associated with higher tumor grade, higher T stage, nodal positivity, ER and PR negativity, and HER2 positivity (all p&lt;0.001). In univariate analyses, overall, breast cancer specific, disease-free and distant disease-free survival (OS, BCSS, DFS, DDFS) were significantly shorter in DTC positive patients with p-values of &lt;0.001. Multivariate analyses showed the DTC status to be an independent prognostic marker for OS, BCSS, DFS and DDFS with hazard ratios (HR) and 95%-confidence intervals (CI) of 1.23 (95%-CI: 1.06-1.42, p=0.007), 1.38 (95%-CI: 1.11-1.72, p=0.004), 1.29 (95%-CI: 1.10-1.50, p=0.001) and 1.32 (95%-CI: 1.10-1.58, p=0.003), respectively.
Conclusions
Detection of DTC in the bone marrow is an independent prognostic marker in patients with non-metastatic breast cancer. Further studies should investigate the impact of DTC on metastatic cancer progression and their role for clinical decision making.
Citation Format: Hartkopf AD, Brucker SY, Taran F-A, Harbeck N, von Au A, Naume B, Pierga J-Y, Hoffmann O, Beckmann MW, Rydén L, Fehm T, Aft R, Montserrat S, Walter V, Rack B, Schuetz F, Borgen E, Ta M-H, Bittner A-K, Fasching P, Fernö M, Krawczyk N, Weilbaecher K, Margelí M, Hahn M, Jueckstock J, Domschke C, Bidard F-C, Kasimir-Bauer S, Schoenfisch B, Kurt AG, Wallwiener M, Gebauer G, Wallwiener D, Janni W, Pantel K. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-07.