Abstract P4-01-01: Presence of circulating tumor cells in high-risk early breast cancer do not predict site of metastatic lesions - Results of the SUCCESS A trial
Authors: Elisabeth Katharina Trapp, Peter A Fasching, Tanja Fehm, Andreas Schneeweiss, Volkmar Mueller, Nadia Harbeck, R. Lorenz, Claudia Schumacher, Georg Heinrich, Amelie deGregorio deGregorio, Marie Tzschaschel, Inga Bekes, Christoph Scholz, Brigitte Rack, Wolfgang Janni, Thomas WP Friedl
Journal: Cancer Research (2020)

Abstract Background: The prognostic relevance of circulating tumor cells (CTCs) during adjuvant breast cancer treatment and follow up has been well established. However, little information is available regarding CTC-detection and its association to site of first metastatic disease. Methods: The adjuvant phase III SUCCESS A trial, an open label, randomized, multicenter study, compared chemotherapy with three cycles of epirubicin, fluorouracil and cyclophosphamide followed by either three cycles of docetaxel or three cycles of docetaxel plus gemcitabine in patients with early high-risk breast cancer. Following chemotherapy, patients were randomized to two or five years of zoledronate treatment. CTC status was assessed before and after chemotherapy using the FDA-approved CellSearch® System (Menarini Silicon Biosystems; Bologna, Italy). The association between the presence of CTCs and the site of first distant disease was assessed using Chi Square tests. Findings: Of 3754 SUCCESS A patients, 373 developed metastatic disease. 206 of these patients participated in the translational research program of the trial so the CTC status at baseline was assessed. These patients were included into the analysis. At least one CTC before chemotherapy was detected in 70 (34.0%) of patients (median 2 CTCs, range 1 - 827 CTCs). For 159 patients, CTC status after chemotherapy could also be evaluated. Disease progression in terms of first distant disease occurred in 44 patients (21.4 %) in the bones, in 60 (29.1 %) in visceral sites (lung, liver), in 23 (11.2 %) in the brain or neural system, and in 51 patients (24.7 %) in other sites. In 28 patients (13.6 %), more than one site of metastatic disease was overt at the time of first distant recurrence. The median time to metastatic disease (measured from date of randomization) was 33.0 months (range 0.7 - 92.4 months). Overall, patients with bone-only first distant disease were numerically most likely to be CTC positive before chemotherapy (40.9 %); however, there was no significant association between site of first metastatic disease (bones, visceral, other) and the presence of CTCs before chemotherapy (p.224). Adding CTC status after chemotherapy did not change the results. However, patients with persistently positive CTCs were significantly more likely to show first distant disease at multiple sites than patients with a negative CTC status before and/or after chemotherapy. Interpretation: Although the presence of CTCs predicts poor prognosis in early breast cancer, no association of positive CTC status before and after chemotherapy with the site of metastatic disease was found. Therefore, a positive CTC status should trigger routine diagnostic intervention depending on clinical evaluation. Citation Format: Elisabeth Katharina Trapp, Peter A Fasching, Tanja Fehm, Andreas Schneeweiss, Volkmar Mueller, Nadia Harbeck, R. Lorenz, Claudia Schumacher, Georg Heinrich, Amelie deGregorio deGregorio, Marie Tzschaschel, Inga Bekes, Christoph Scholz, Brigitte Rack, Wolfgang Janni, Thomas WP Friedl. Presence of circulating tumor cells in high-risk early breast cancer do not predict site of metastatic lesions - Results of the SUCCESS A trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-01.