Abstract P4-01-08: Persistence of circulating tumor cells immediately after and two years after systemic adjuvant chemotherapy in patients with early breast cancer – Results of the German SUCCESS trials
Authors: Jaeger Bernadette AS , Andergassen Ulrich , Neugebauer Julia K , Alunni-Fabbroni Marianna , Melcher Carola A , Hagenbeck Carsten , Albrecht Susanne , Lorenz Ralf , Decker Thomas , Heinrich Georg , Fehm Tanja , Schneeweiss Andreas , Beckmann Matthias W , Pantel Klaus , Friese Klaus , Fasching Peter A , Friedl Thomas WP , Janni Wolfgang , Rack Brigitte K 
Published: May 2015

Abstract
Background
There is growing evidence that circulating tumor cells (CTCs) have prognostic impact in patients (pts) with early breast cancer (EBC). In this study the persistence of CTCs immediately after and two years after chemotherapy (Ctx) was prospectively evaluated according to molecular subtypes within the German multicentre SUCCESS trials.
Methods
SUCCESS A and C were randomized Phase III studies including pts with node positive or high-risk node negative EBC. In each trial two different adjuvant Ctx regimen were compared: FEC-DOC (3 cycles of FEC followed by 3 cycles of Docetaxel) to FEC-DG (3 cycles of FEC followed by 3 cycles of Docetaxel/Gemcitabine) in SUCCESS A and in the SUCCESS C study FEC-DOC to an anthracycline-free Ctx regimen (6 cycles of Docetaxel/Cyclophosphamide). Both studies involved a second randomization after Ctx: 2 vs. 5 years of zoledronic acid treatment (SUCCESS A) or 2-years of an individualized lifestyle-intervention program vs. general lifestyle recommendations (SUCCESS C). Adequate endocrine treatment and treatment with trastuzumab as indicated were included in both trials.
As part of the translational research program, 23ml of peripheral blood were drawn to isolate CTCs using the CellSearch System (Veridex, USA). After immunomagnetic enrichment with an anti-EpCam-antibody, cells were labelled with anti-CK8/18/19 and anti-CD45 antibodies to distinguish epithelial cells from leucocytes. The cut-off for CTC-positivity was ≥ 1 CTC.
Molecular subtypes were defined as luminal-A-like (hormone-receptor positive, G1 or 2), luminal-B-like (hormone-receptor positive, G3), HER2-positive and triple-negative.
Results
CTC analyses were performed for 3344 blood samples collected immediately after Ctx and for 1352 blood samples two years after Ctx. After Ctx 17.5% (584/3344) of the pts were CTC-positive (range 1 – 124 CTCs), and two years after Ctx the positivity rate for CTCs was 17.2% (233/1352, range 1-99).
CTC positivity as assessed immediately after Ctx differed significantly among molecular subtypes (chi-square test, p &lt; 0.001): Pts with HER2-positive tumors were more likely to have CTCs in the blood (26.3%, 105/400) as compared to pts with luminal-A-like tumors (15.4%, 283/1842), luminal-B-like tumors (17.7%, 142/802), or triple-negative tumors (18.0%, 54/300).
Two years after Ctx CTC-positivity did not differ significantly among molecular subtypes (chi-square test, p = 0.463). CTC-positivity rates were 15.7% (96/613) for luminal-A-like tumors, 19.1% (49/256) for luminal-B-like tumors, 17.2% (51/296) for HER2-positive tumors, and 19.8% (37/187) for triple-negative tumors.
Conclusions
The data of this study confirm previous findings that CTCs may persist after standard adjuvant therapy. Immediately after Ctx CTCs seem to be more frequent in pts with HER2-positive tumors as compared to other molecular subtypes, while two years after Ctx no differences in CTC positivity among molecular subtypes were detected. These results might indicate good efficacy of HER2-targeted therapies on CTCs.
Citation Format: Bernadette AS Jaeger, Ulrich Andergassen, Julia K Neugebauer, Marianna Alunni-Fabbroni, Carola A Melcher, Carsten Hagenbeck, Susanne Albrecht, Ralf Lorenz, Thomas Decker, Georg Heinrich, Tanja Fehm, Andreas Schneeweiss, Matthias W Beckmann, Klaus Pantel, Klaus Friese, Peter A Fasching, Thomas WP Friedl, Wolfgang Janni, Brigitte K Rack. Persistence of circulating tumor cells immediately after and two years after systemic adjuvant chemotherapy in patients with early breast cancer – Results of the German SUCCESS trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-08.