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BMC Cancer. 2015 Jul 15;15:519. doi: 10.1186/s12885-015-1491-7.

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

Author information

1
Department of General, Visceral, Transplantation, Vascular and Thoraic Surgery, Hospital of the University of Munich, Munich, Germany. khalfter@spherotec.com.
2
Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Munich, Germany. nina.ditsch@med.uni-muenchen.de.
3
Marienhospital Bottrop, Bottrop, Germany. hans-christian.kolberg@mhb-bottrop.de.
4
Evangelische Kliniken Gelsenkirchen, Gelsenkirchen, Germany. fischer@evk-ge.de.
5
Klinikum St. Marien Amberg, Amberg, Germany. hauzenberger.tanja@klinikum-amberg.de.
6
Department of Obstetrics and Gynecology, Klinikum Dritter Orden, Munich, Germany. franz.koch@dritter-orden.de.
7
Klinikum Landshut, Landshut, Germany. ingo.bauerfeind@klinikum-landshut.de.
8
GBG Forschungs GmbH, Neu-Isenburg and University Women's Hospital Frankfurt, Frankfurt, Germany. gunter.vonminckwitz@germanbreastgroup.de.
9
SpheroTec GmbH, Martinsried, Germany. ifunke@spherotec.com.
10
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. cri@ibe.med.uni-muenchen.de.
11
Department of General, Visceral, Transplantation, Vascular and Thoraic Surgery, Hospital of the University of Munich, Munich, Germany. Barbara.mayer@med.uni-muenchen.de.
12
SpheroTec GmbH, Martinsried, Germany. Barbara.mayer@med.uni-muenchen.de.

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.

PMID:
26169261
PMCID:
PMC4501185
DOI:
10.1186/s12885-015-1491-7
[Indexed for MEDLINE]
Free PMC Article

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