Page 52 - SDIR5 Abstract book 21 12 2021.
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POSTER PRESENTATIONS



               P12


                  A novel triple negative lipid rich breast cancer (TN/LRBC) patient derived xenograft (PDX)

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                Irida Papapostolou , Evangelia Sereti , Evangelia Bouloutsou , Vasileios Konteles ,Fani Koutsougianni ,
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                Andromachi Lambrianidou , Antigoni Poultsidi , Maria Ioannou , Aspasia Tsezou , Konstantinos Dimas
                  1 Department of Pharmacology,  Laboratory of Cytogenetics and Molecular Genetics,  Department of Surgery,
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                               5 Department of Pathology, School of Medicine, University of Thessaly, Greece.
                        2 Department of Translational Medicine, Division of Urological Cancers, Lund University, Sweden

               Background: Lipid-rich breast cancer (LRBC) is a rare subtype of breast cancer, highly metastatic and with
               poor prognosis. It is reported to generally be negative for ER/PR receptors but highly positive for HER2
               expression with triple negative (TN) cancers to be even rarer. Noteworthy, there are no models available
               for studies on this rare type of cancer so far. Our aim was to establish and characterize a PDX from a patient
               with TN/LRBC. Materials and methods: The model was developed in immunocompromised mice after direct
               engraftment  of  tumor  fragments  surgically  excised  from  the  patient.  The  PDX  was  further  evaluated
               pharmacologically following patient’s schedule. Histological, karyotypic and NGS analysis were performed
               for  the  first  time  for  this  type  of  cancer.  Results:  Pharmacological  characterization  revealed  that  the
               xenograft responded well to cyclophosphamide and docetaxel, as was expected, but doxorubicin was found
               to be highly toxic. As an alternative Caelyx® (stealth liposomal doxorubicin) was for the first time tested on
               this  type  of  breast  cancer  and  found  to  be  highly  efficient  with  lower  toxicity.  Karyotyping  revealed
               polyploidy, while NGS analysis the presence of a pathogenic mutation in the MSH2 gene (c.482T> A, p.
               Val161Asp)  in  both  the  patient  and  the  xenograft.    Data  suggest  that  this  mutation  may  be  a  driver
               mutation. Conclusion: This is the first report on the development of a PDX for TN/ LRBC, a model that we
               anticipate will be an extremely valuable tool towards developing novel treatments and understanding the
               biology of this rare type of breast cancer.
               Keywords: Triple negative lipid rich breast cancer, patient derived xenograft, liposomal doxorubicin
               Acknowledgment: This research has been co-financed by the European Union and Greek national funds
               through  the  Operational  Program  Competitiveness,  Entrepreneurship  and  Innovation,  under  the  call
               RESEARCH – CREATE – INNOVATE  (project code:T1EDK-01833)












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