Link to PDF (annalsofoncology.org)
233P – Breast Cancer Organoids Mimic Disease Heterogeneity, Allow High-Throughput Drug Screening and Show Correlation with Clinical Response
Breast cancer (BC) is a highly heterogeneous disease; therefore, it is urgent to identify an ex vivo model that accurately mimics the heterogeneity. Patient-derived organoids (PDOs) represent an ideal preclinical model for human tumors, thus facilitating the translation of basic cancer research to clinical practice by assessing drug responses in a personalized fashion.
The Onco-PDO® test by Invitrocue analyses the drug response of chemotherapeutics on PDOs generated from surgical samples or core needle biopsies. In addition, PDOs are further expanded and analyzed histologically and genomically. Furthermore, the clinical follow-up data are collected and correlated with the PDO drug response.
We describe the results of our ongoing prospective exploratory study to establish and evaluate Onco-PDO® testing in breast cancer patients. The study comprises two cohorts. Up to date, we received 71 tumor tissues from the primary tumor (PT; n=55) and lymph node metastases (LN; n=16). The PDO success rate stands at 90%. So far, the test was successfully performed in 73% of cases, failed in 21%, and in 6% of cases the test is in progress. The success rate of the test from PT-PDOs was higher than LN-PDOs (80% versus 50%), possibly due to the higher tumor cell fraction in the PT tissue. PDOs recapitulate the histological and genetic characteristics of the matched patient tumors. So far, from patients receiving neoadjuvant chemotherapy 18 were analyzed for in vivo/in vitro correlation. The correlation of the PDO drug response with the clinical outcomes stands at 78% (n=14/18), with a 76% positive predictive value (n=13/17), and in one refractory patient the Onco-PDO® test predicted the treatment failure correctly; however, a descriptive statistic is not feasible.
We have established a biorepository of BC PDOs indicating the spectrum of BC’s histology and genetic diversity and treatment response. PDOs mimicking the patient-specific and clinically relevant responses to chemotherapy might facilitate determining new and more personalized treatments for individual BC patients. Our results support the translation of BC PDOs to the clinic as an ex vivo therapeutic platform for drug screening.
Legal entity responsible for the study
Interdisziplinäres Brustzentrum, Klinik und Poliklinik für Frauenheilkunde Technische Universität München (Dr. Stefan Paepke) and Invitrocue Europe AG Interdisziplinäres Brustzentrum, Klinik und Poliklinik für Frauenheilkunde Technische Universität München.
Invitrocue Europe AG.
K. Steiger: Financial Interests, Institutional, Other, Consultancy: Roche Pharma AG; Financial Interests, Personal, Advisory Board: TRIMT GmbH. N. Pfarr: Financial Interests, Personal, Invited Speaker: Illumina, Novartis, Bayer, Roche, AstraZeneca, Thermo Fisher Scientific, Bristol Myers Squib; Financial Interests, Personal, Advisory Board: Novartis, Lilly; Financial Interests, Personal, Other, Traveling Support: Bristol Myers Squib; Non-Financial Interests, Institutional, Product Samples: Illumina, Thermo Fisher Scientific. M. Kiechle: Financial Interests, Personal, Other, Renumeration: Springer Press, Biermann Press, Celgene, AstraZeneca, Myriad Genetics, Teva, Eli Lilly, GSK; Financial Interests, Personal, Advisory Role: Myriad Genetics, Bavarian KVB, DKMS Life, Blaek, Teva, Exeltis; Financial Interests, Personal, Ownership Interest: Therawis Diagnostic GmbH, AIM GmbH; Financial Interests, Personal, Funding: Sphingotec, Deutsche Krebshilfe, DFG, Senator Roesner Foundation, Dr. Pommer-Jung Foundation, Waltraut Bergmann Foundation, Bavarian State Ministry of Economy, BMBF, Innovation. K. Lindner: Financial Interests, Personal, Stocks/Shares: Invitrocue. C. Peschel: Financial Interests, Personal, Advisory Role, Consultant: Invitrocue. W. Weichert: Financial Interests, Personal, Advisory Board, Speakers Bureau and Advisory Boards: Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Amgen, Astellas, Eisai, Johnson&Johnson, Janssen, Illumina, Siemens, Agilent, ADC, GSK and Molecular Health; Financial Interests, Institutional, Research Grant: Roche, MSD, BMS, AstraZeneca. S. Paepke: Financial Interests, Personal, Advisory Board, Consultant: PFM Medical AG Cologne Germany; Financial Interests, Personal, Invited Speaker, Consultant: Novusscientific Sweden, Triconmed Germany, Sysmex Germany, Sysmex Europek, Neodynamics Sweden, MBN Germany, Invitrocue Europe GmbH, Dynamesh Germany; Financial Interests, Institutional, Funding, Scientific Grant: RTI Surgical; Financial Interests, Institutional, Invited Speaker, Scientific grant: PFM Medical, Novusscientific Sweden; Non-Financial Interests, Project Lead, Workshops/Masterclass for colleagues in Reconstructive Breast Surgery: Roche, Grenzach Whylen Germany, Sysmex Germany; Non-Financial Interests, Project Lead, Workshops for colleagues in Reconstructive Breast Surgery: Philips GmbH Germany, Triconmed Germany. All other authors have declared no conflicts of interest.