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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Most breast cancer patients receive chemotherapy as part of their treatment. Unfortunately, treatment outcomes cannot be predicted with the current methods. Therefore, in the preset study, we explore the feasibility of a functional sensitivity test for the chemotherapeutic agents cisplatin and docetaxel on breast cancer tissue slices in culture. We show that these two agents need to be analyzed differently; cisplatin treatment resulted in cell death and a reduction in proliferation, whereas docetaxel could be assessed by determining the relative numbers of cells in mitosis. We also took the next step towards clinic application by adapting this test for biopsies from metastatic breast tumors. This test is now ready for a direct evaluation of its predictive value in clinical trials.

Abstract

Background chemotherapy is part of most breast cancer (BC) treatment schedules. However, a substantial fraction of BC tumors does not respond to the treatment. Unfortunately, no standard biomarkers exist for response prediction. Therefore, we aim to develop ex vivo sensitivity assays for two types of commonly used cytostatics (i.e., platinum derivates and taxanes) on organotypic BC tissue slices. Methods: Ex vivo cisplatin sensitivity assays were established using organotypic tissue slices derived from the surgical resection material of 13 primary BCs and 20 fresh histological biopsies obtained from various metastatic sites. Furthermore, tissue slices of 10 primary BCs were used to establish a docetaxel ex vivo sensitivity assay. Results: Cisplatin sensitivity was assessed by tissue morphology, proliferation and apoptosis, while the relative increase in the mitotic index was discriminative for docetaxel sensitivity. Based on these read-outs, a scoring system was proposed to discriminate sensitive from resistant tumors for each cytostatic. We successful completed the cisplatin sensitivity assay on 12/16 (75%) biopsies as well. Conclusions: We developed an ex vivo cisplatin and docetaxel assay on BC slices. We also adapted the assay for biopsy-sized specimens as the next step towards the correlation of ex vivo test results and in vivo responses.

Details

Title
Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer
Author
Ladan, Marjolijn M 1 ; Meijer, Titia G 1   VIAFID ORCID Logo  ; Verkaik, Nicole S 1 ; Komar, Zofia M 2 ; Carolien H M van Deurzen 3 ; den Bakker, Michael A 4 ; Kanaar, Roland 1 ; van Gent, Dik C 1   VIAFID ORCID Logo  ; Jager, Agnes 5 

 Department of Molecular Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands; [email protected] (M.M.L.); [email protected] (T.G.M.); [email protected] (N.S.V.); [email protected] (Z.M.K.); [email protected] (R.K.); Oncode Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands 
 Department of Molecular Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands; [email protected] (M.M.L.); [email protected] (T.G.M.); [email protected] (N.S.V.); [email protected] (Z.M.K.); [email protected] (R.K.) 
 Department of Pathology, Erasmus MC Cancer Institute, 3000 CA Rotterdam, The Netherlands; [email protected] 
 Department of Pathology, Maasstad Ziekenhuis, 3007 AC Rotterdam, The Netherlands; [email protected] 
 Department of Medical Oncology, Erasmus MC Cancer Institute, 3000 CA Rotterdam, The Netherlands; [email protected] 
First page
1252
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2637614955
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.