Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – the SpheroNEO study

BMC Cancer

Research Article

Kathrin Halfter¹  Barbara Mayer²  Franz Edler von Koch³  Nina Ditsch⁴  Holger Fischer⁵  Gunter von Minckwitz⁶  Alexander Crispin⁷  Ingo Bauerfeind⁸  Tanja Hauzenberger⁹  Hans-Christian Kolberg^1,10  Ilona Funke^1,11 

[1] Department of General, Visceral, Transplantation, Vascular and Thoraic Surgery, Hospital of the University of Munich, Munich, Germany;Department of General, Visceral, Transplantation, Vascular and Thoraic Surgery, Hospital of the University of Munich, Munich, Germany;SpheroTec GmbH, Martinsried, Germany;Department of Obstetrics and Gynecology, Klinikum Dritter Orden, Munich, Germany;Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Munich, Germany;Evangelische Kliniken Gelsenkirchen, Gelsenkirchen, Germany;GBG Forschungs GmbH, Neu-Isenburg and University Women’s Hospital Frankfurt, Frankfurt, Germany;IBE LMU, Department of Obstetrics and Gynecology, Technical University of Munich, Klinikum Starnberg, Leopoldina Krankenhaus der Stadt Schweinfurt, Markus Krankenhaus Frankfurt, Klinikum Nürnberg, Städtisches Klinkum Karlsruhe, Klinikum Harlaching, Munich, Germany;Klinikum Landshut, Landshut, Germany;Klinikum St. Marien Amberg, Amberg, Germany;Marienhospital Bottrop, Bottrop, Germany;SpheroTec GmbH, Martinsried, Germany;

关键词: Breast cancer;    Neoadjuvant chemotherapy;    Predicting treatment outcome;    Cellular response to anticancer drugs;    Personalized medicine;    in vitro diagnostics;   

DOI  :  10.1186/s12885-015-1491-7

 received in 2014-09-09, accepted in 2015-06-16,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAim of this prospective study was to predict response to neoadjuvant therapy in breast cancer patients using an in vitro breast cancer spheroid model.MethodsThree-dimensional spheroids were directly generated from fresh breast tumor biopsies of 78 patients eligible for neoadjuvant therapy. Cell survival was measured after in vitro exposure to the equivalent therapeutic agents in the breast cancer spheroid model. Treatment results in vitro were correlated with pathological complete response (pCR, i.e. ypT0 ypN0) determined at surgery.ResultsA mean cell survival of 21.8 % was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8 % in 56 patients without pCR (P = .001). The area under the receiver operator characteristic curve to predict pCR was 0.86 (95 % CI: 0.77 to 0.96) for cell survival in vitro compared to 0.80 (95 % CI: 0.70 to 0.90) for a combined model of conventional factors (hormone- and HER2 receptor, and age). A cutoff at 35 % cell survival for the spheroid model was proposed. Out of the 32 patients with values below this threshold, 21 patients (65.6 %) and one patient (2.2 %) with a cell survival greater than 35 % achieved pCR respectively; (sensitivity 95.5 % (95 % CI: 0.86 to 1.00); specificity 80.4 % (95 % CI: 0.70 to 0.91)). Extent of residual disease positively correlated with increased cell survival (P = .021).ConclusionThe breast cancer spheroid model proved to be a highly sensitive and specific predictor for pCR after neoadjuvant chemotherapy in breast cancer patients.

【 授权许可】

Unknown   
© Halfter et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.