Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer

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.