Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis-Results from the Adjuvant SUCCESS A Trial

Elisabeth K Trapp; Peter A Fasching; Tanja Fehm; Andreas Schneeweiss; Volkmar Mueller; Nadia Harbeck; Ralf Lorenz; Claudia Schumacher; Georg Heinrich; Fabienne Schochter; Amelie de Gregorio; Marie Tzschaschel; Brigitte Rack; Wolfgang Janni; Thomas W P Friedl

doi:10.3390/cancers14163949

Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis-Results from the Adjuvant SUCCESS A Trial

Cancers (Basel). 2022 Aug 16;14(16):3949. doi: 10.3390/cancers14163949.

Authors

Affiliations

¹ Department of Gynecology and Obstetrics, Medical University of Graz, 8036 Graz, Austria.
² Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
³ Department of Gynecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, 40225 Düsseldorf, Germany.
⁴ National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, 69120 Heidelberg, Germany.
⁵ Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
⁶ Breast Center, Department of Gynecology and Obstetrics and CCC Munich, LMU University Hospital, 81337 München, Germany.
⁷ Gynecologic Practice Dr. Lorenz, N. Hecker, Dr. Kreiss-Sender, 38100 Braunschweig, Germany.
⁸ Department of Gynecology and Obstetrics, St. Elisabeth's Hospital, 50935 Cologne, Germany.
⁹ Oncological Practice, 15517 Fürstenwalde, Germany.
¹⁰ Department of Gynecology and Obstetrics, University Hospital Ulm, 89081 Ulm, Germany.

Abstract

The prognostic relevance of circulating tumor cells (CTCs) in breast cancer is well established. However, little is known about the association of CTCs and site of first metastasis. In the SUCCESS A trial, 373 out of 3754 randomized high-risk breast cancer patients developed metastatic disease. CTC status was assessed by the FDA-approved CellSearch^®-System (Menarini Silicon Biosystems, Bologna, Italy) in 206 of these patients before chemotherapy and additionally in 159 patients after chemotherapy. CTCs were detected in 70 (34.0%) of 206 patients before (median 2 CTCs, 1-827) and in 44 (27.7%) of 159 patients after chemotherapy (median 1 CTC, 1-124); 16 (10.1%) of 159 patients were CTC-positive at both timepoints. The site of first distant disease was bone-only, visceral-only, and other-site-only in 44 (21.4%), 60 (29.1%), and 74 (35.9%) patients, respectively, while 28 (13.6%) patients had multiple sites of first metastatic disease. Patients with CTCs at both timepoints more often showed bone-only first distant disease (37.5% vs. 21.0%) and first distant disease at multiple sites (31.3% vs. 12.6%) than patients without CTCs before and/or after chemotherapy (p = 0.027). In conclusion, the presence of CTCs before and after chemotherapy is associated with multiple-site or bone-only first-distant disease and may trigger intensified follow-up and perhaps further treatment.

Keywords: breast cancer; circulating tumor cells (CTC); liquid biopsy; metastasis.

Grants and funding

Financial support for the SUCCESS A study was provided by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, Sanofi-Aventis.