Abstract P1-01-03: Dynamics of circulating tumor cells during the course of chemotherapy and prognostic relevance across molecular subtypes in high-risk early breast cancer patients – Results from the adjuvant SUCCESS A trial
Authors: Tzschaschel MLJ , Rack B , Andergassen U , Friedl TWP , Schneeweiss A , Mueller V , Tanja F , Pantel K , Gade J , Lorenz R , Rezai M , Tesch H , Soeling U , Polasik A , Alunni-Fabbroni M , Trapp EK , Mahner S , Schindlbeck C , Lichtenegger W , Beckmann MW , Fasching PA , Janni W 
Published: March 2017

Background: The presence of circulating tumor cells (CTCs) before chemotherapy is known to be associated with reduced disease free survival (DFS) and overall survival (OS) in early breast cancer (EBC). In addition, recent findings suggest that CTCs persisting after adjuvant chemotherapy indicate poor prognosis. In an explorative analysis of the SUCCESS A trial, we evaluated the prognostic relevance of changes in CTC counts during the course of adjuvant chemotherapy across molecular subtypes to assess whether the prognostic role of persisting CTCs varies according to tumor biology.

Methods: The SUCCESS A trial is a phase III study, where patients with high-risk EBC (stage pN1-3 or pT2-4 or grade 3 or age ≤ 35 or hormone-receptor negative) were randomized to adjuvant chemotherapy with 3 cycles of epirubicin-fluorouracil-cyclophosphamide followed by either 3 cycles of docetaxel or 3 cycles of gemcitabine-docetaxel. CTC enumeration was performed before and after chemotherapy using the FDA-approved CellSearch® System (Janssen Diagnostics, LLC), and CTC positivity was defined as ≥ 1 CTC in 23 ml blood. Molecular subtypes were defined as luminal A like (hormone-receptor positive, grading 1 or 2), luminal B like (hormone-receptor positive, grading 3), triple-negative or HER2-positive. Patient outcome in terms of DFS and OS was analyzed using univariate log-rank tests and Cox regression models (median follow-up time 65.2 months).

Results: Data on both molecular subtypes and CTC status before and after chemotherapy were available for 1485 (39.6%) of 3754 patients randomized. This cohort contained 577 (38.9%) luminal A like, 236 (15.9%) luminal B like, 379 (25.5%) HER2-positive and 293 (19.7%) triple negative tumors. Overall, 917 (61.8%) patients were CTC negative before and after chemotherapy (neg/neg), 260 (17.5%) patients had a negative CTC status before and a positive CTC status after chemotherapy (neg/pos), 229 (15.4%) patients converted from positive to negative CTC status (pos/neg), and 79 (5.3%) patients were positive for CTCs at both time points (pos/pos). There were significant differences in DFS and OS among these four groups in patients with luminal A like tumors (log rank test, both p &lt; 0.003) and patients with luminal B like tumors (log rank test, both p &lt; 0.001). In both patients with luminal A like or luminal B like tumors, persistently CTC positive patients had the worst outcome (relative to persistently CTC-negative patients) in terms of DFS and OS. In contrast to luminal-like tumors, no significant differences with regard to DFS or OS were found among the four groups (neg/neg, neg/pos, pos/neg, pos/pos) in patients with HER2-positive or triple-negative tumors (log rank test, all p &gt; 0.13).

Conclusion: The presence of CTCs both before and after adjuvant chemotherapy was associated with poor survival in luminal A like and luminal B like tumors, but not in HER2-positive or triple-negative tumors. Further research is needed to evaluate the effect of chemotherapy on CTC prevalence in different molecular subtypes of EBC.

Citation Format: Tzschaschel MLJ, Rack B, Andergassen U, Friedl TWP, Schneeweiss A, Mueller V, Tanja F, Pantel K, Gade J, Lorenz R, Rezai M, Tesch H, Soeling U, Polasik A, Alunni-Fabbroni M, Trapp EK, Mahner S, Schindlbeck C, Lichtenegger W, Beckmann MW, Fasching PA, Janni W. Dynamics of circulating tumor cells during the course of chemotherapy and prognostic relevance across molecular subtypes in high-risk early breast cancer patients – Results from the adjuvant SUCCESS A trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-03.