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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Kathrin Halfter, Nina Ditsch, Hans-Christian Kolberg, Holger Fischer, Tanja Hauzenberger, Franz Edler von Koch, Ingo Bauerfeind, Gunter von Minckwitz, Ilona Funke, Alexander Crispin, Barbara Mayer, Behalf of the SpheroNEO Study Group

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Aim of this prospective study was to predict response to neoadjuvant therapy in breast cancer patients using an in vitro breast cancer spheroid model.

Methods

Three-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.

Results

A 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).

Conclusion

The breast cancer spheroid model proved to be a highly sensitive and specific predictor for pCR after neoadjuvant chemotherapy in breast cancer patients.
Appendix
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Metadata
Title
Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – the SpheroNEO study
Authors
Kathrin Halfter
Nina Ditsch
Hans-Christian Kolberg
Holger Fischer
Tanja Hauzenberger
Franz Edler von Koch
Ingo Bauerfeind
Gunter von Minckwitz
Ilona Funke
Alexander Crispin
Barbara Mayer
Behalf of the SpheroNEO Study Group
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1491-7

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