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Prognostic Impact of Circulating Tumor Cells for Breast Cancer Patients Treated in the Neoadjuvant "Geparquattro" Trial

Sabine Riethdorf, Volkmar Müller, Sibylle Loibl, Valentina Nekljudova, Karsten Weber, Jens Huober, Tanja Fehm, Iris Schrader, Jörn Hilfrich, Frank Holms, Hans Tesch, Christian Schem, Gunter Von Minckwitz, Michael Untch & Klaus Pantel

abstract This study aimed to evaluate the prognostic impact of circulating tumor cells (CTC) detected in patients with operable or locally advanced breast cancer before and after neoadjuvant therapy (NT) within the clinical trial GeparQuattro. Data on CTCs enumerated with the CellSearch system were available for 213 and 207 patients before and after NT, respectively. Associations of CTCs with disease-free survival (DFS) and overall survival (OS) were analyzed by nonparametric Kaplan-Meier estimates and parametric Cox regression. After a median follow-up of 67.1 months, the detection of ≥1 CTC/7.5 mL and ≥2 CTCs/7.5 mL before NT was associated with reduced DFS ( = 0.031 and < 0.0001, respectively) and OS ( = 0.0057 and < 0.0001, respectively), whereas CTCs detected after NT did not correlate with DFS or OS. In parametric univariate and multivariate Cox models, ≥1 CTC/7.5 mL, ≥2 CTCs/7.5 mL, and absolute CTC numbers before NT revealed to be independent prognostic parameters of DFS and OS. CTC-negative patients with pathologic complete response (pCR) exhibited the best prognosis, whereas those with CTCs and less tumor response were at high risk of tumor relapse. In HER2 (ERBB2)-positive and triple-negative patients, ≥2 CTCs/7.5 mL detected before NT also were significantly associated with worse DFS and OS. Detection of CTCs before NT is an independent prognostic factor of impaired clinical outcome, and combined with pCR, it could be helpful to stratify breast cancer patients for therapeutic interventions. .
   
citation Riethdorf S, Müller V, Loibl S, Nekljudova V, Weber K, Huober J, Fehm T, Schrader I, Hilfrich J, Holms F, Tesch H, Schem C, von Minckwitz G, Untch M, Pantel K. Prognostic Impact of Circulating Tumor Cells for Breast Cancer Patients Treated in the Neoadjuvant "Geparquattro" Trial. Clin Cancer Res 2017; 23:5384-5393.
   
type journal paper/review (English)
date of publishing 05-07-2017
journal title Clin Cancer Res (23/18)
ISSN electronic 1557-3265
pages 5384-5393
PubMed 28679772
DOI 10.1158/1078-0432.CCR-17-0255