Abstract P4-01-03: Prognostic relevance of circulating tumor cells across different molecular subgroups in the adjuvant SUCCESS-A study
Authors: Janni Wolfgang , Schneeweiss Andreas , Häberle Lothar , Fasching Peter A , Schwentner Lukas , Rezai Mahdi , Hilfrich Jörn , Tesch Hans , Heinrich Georg , Forstbauer Helmut , Friedl Thomas , Schochter Fabienne , Albrecht Susanne , Jäger Bernadette , Jückstöck Julia , Fehm Tanja , Müller Volkmar , Friese Klaus , Lichtenegger Werner , Beckmann Matthias B , Rack Brigitte 
Published: May 2015

Abstract
Aim: The prognostic value of circulating tumor cells (CTCs) in the adjuvant setting has recently been demonstrated in the SUCCESS A Study (Rack et al. JNCI 2014). As breast carcinomas depend on partly different pathways for progression, the relevance of CTCs could differ between molecular intrinsic subtypes of breast cancer. Aim of this study was therefore to analyze the prognostic impact of CTCs in molecular subtypes of a large patient cohort.
Methods: Within the adjuvant SUCCESS A Study, patients were treated either with 5-Flourouracil, Epirubicin and Cyclophosphamid (FEC) followed by Docetaxel (D) or with FEC followed by D and Gemcitabine (DG). There was no restriction with regard to molecular subtype, however a high recurrence risk was required for study entry. In addition patients were assessed prospectively for the presence of CTCs before chemotherapy. Molecular subtypes were defined as: triple negative (TN), hormone receptor positive and grading 1/2 (LUM A like), hormone receptor positive and grading 3 (LUM B like), HER2 positive (HER2 like). We studied whether the addition of CTC status (0 CTC vs &gt; 0 CTCs) to well-known predictors such as age, BMI, tumor size, lymph node status improved the prediction of overall survival (OS) and disease free survival (DFS) across all patients and especially within molecular subtypes using likelihood ratio tests, which compared multivariable Cox regression models with and without CTC and the interaction between CTC and molecular subtype.
Results: Information about molecular subtype and CTCs was available in a total of 1994 patients. At least one CTC was seen in 422 (21.2%) of patients. 383 (19.2%) were TN, 798 were LUM A like (40.0%), 328 (16.4%) were LUM B like (16.4%) and 485 (24.3%) were HER2 like. The effect of CTC on overall survival had a HR of 2.50 (95%: 1.75 to 3.58) for the entire cohort. However as the effect was different across subtypes (p=0.04, likelihood ratio test), subtype specific HR were calculated. The effects on OS were most prominent in LUM B like patients (HR=3.96; 95%CI: 1.93 to 8.14) and LUM A like patients (HR=3.57; 95%CI: 1.81 to 7.03), less strong in HER2 like (HR=2.35; 95%CI: 1.04 to 5.32) and not present in TN patients (HR=1.18; 95%CI: 0.62 to 2.24). CTC status had a clear effect on DFS as well (HR=1.93, 95%CI: 1.48 to 2.52). It could not be shown that this effect was different across subtypes (p=0.07, likelihood ratio test). However, the effect size was similarly distributed like the ones for OS.
Conclusion: With regard to OS the prognostic effect of CTCs in this study cohort seems most prominent in patients with hormone receptor positive disease. It is still significant in HER2 positive, but not in TN breast cancer patients. Results with regard to DFS trended into the same direction, differences within subgroups could however not be shown, possibly due to power reasons.
Citation Format: Wolfgang Janni, Andreas Schneeweiss, Lothar Häberle, Peter A Fasching, Lukas Schwentner, Mahdi Rezai, Jörn Hilfrich, Hans Tesch, Georg Heinrich, Helmut Forstbauer, Thomas Friedl, Fabienne Schochter, Susanne Albrecht, Bernadette Jäger, Julia Jückstöck, Tanja Fehm, Volkmar Müller, Klaus Friese, Werner Lichtenegger, Matthias B Beckmann, Brigitte Rack. Prognostic relevance of circulating tumor cells across different molecular subgroups in the adjuvant SUCCESS-A study [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 P4-01-03.