Back to Journals » Cancer Management and Research » Volume 11

First-Line Doublet Chemotherapy for Metastatic Triple-Negative Breast Cancer: Circulating Tumor Cell Analysis of the tnAcity Trial

Authors Liu MC, Janni W, Georgoulias V, Yardley DA, Harbeck N, Wei X, McGovern D, Beck R

Received 2 April 2019

Accepted for publication 14 November 2019

Published 12 December 2019 Volume 2019:11 Pages 10427—10433


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri

Minetta C Liu,1 Wolfgang Janni,2 Vassilis Georgoulias,3 Denise A Yardley,4 Nadia Harbeck,5 Xin Wei,6 Desmond McGovern,7 Robert Beck7

1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; 2Department of Obstetrics and Gynecology, University Clinic Ulm, Ulm, Germany; 3Department of Medical Oncology, School of Medicine, University of Crete, Crete, Greece; 4Department of Medical Oncology, Breast Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN, USA; 5Department of Breast Center, Oncological Therapy and Clinical Trials Unit, University of Munich (LMU), Munich, Germany; 6Department of Translational/Clinical Development, Celgene Corporation, Summit, NJ, USA; 7Department of Clinical Research, Celgene Corporation, Summit, NJ, USA

Correspondence: Minetta C Liu
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Tel +1 507 293 0526

Purpose: Circulating tumor cells (CTCs) are prognostic biomarkers in metastatic breast cancer, but their role in predicting treatment outcomes in metastatic triple-negative breast cancer (mTNBC) is less clear. The tnAcity trial demonstrated a significant progression-free survival (PFS) benefit with nab-paclitaxel (nab-P)/carboplatin (C) over nab-P/gemcitabine (G) or G/C in patients with mTNBC. We assessed the correlation between CTC dynamics and clinical benefit in all patients and by treatment arm.
Methods: CTC enumeration, performed using CELLSEARCH technology (Menarini Silicon Biosystems, Huntingdon Valley, PA, USA), was a prespecified exploratory endpoint in the tnAcity trial. Patients with TNBC were categorized based on pre- and post-treatment CTC levels: Group 1 (+ + +; elevated CTCs at baseline and postbaseline), Group 2 (+ ± ±; CTCs elevated at baseline and cleared postbaseline [cycle 3 and/or cycle 5]), or Group 3 (−; no CTCs detected at baseline). The baseline cutoff was ≥1 CTC/7.5 mL for the main analysis; cutoffs of ≥2 and ≥5 CTCs were used for supporting analyses.
Results: The main analysis included 126 patients (Group 1, n = 24; Group 2, n = 54; and Group 3, n = 48). The median PFS was longer in Group 2 vs Group 1 (8.5 vs 4.7 months; HR, 0.30 [95% CI, 0.17–0.54]). These results were supported by the ≥2- and ≥5-CTC cutoff analyses. The median overall survival rates were 17.8, 16.0, and 9.8 months in Groups 2, 3, and 1, respectively. The overall response rates were 79.6%, 43.8%, and 29.2%, respectively. A numerically higher percentage of patients had CTC clearance during nab-P/C treatment vs nab-P/G or G/C.
Conclusion: Efficacy outcomes trended positively with chemotherapy-induced elimination of CTCs, suggesting that CTC clearance may predict the chemosensitivity of mTNBC tumors.
Trial registration: EudraCT Number: 2013-000113-20; number: NCT01881230.

Keywords: metastatic triple-negative breast cancer, circulating tumor cells, nab-paclitaxel, chemotherapy, prognosis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]