Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study

// Anthony Goncalves 1, 2, * , Francois Bertucci 1, 2, 3, * , Arnaud Guille 2, 3 , Severine Garnier 2, 3 , Jose Adelaide 2, 3 , Nadine Carbuccia 2, 3 , Oliver Cabaud 2, 3 , Pascal Finetti 2, 3 , Serge Brunelle 4 , Gilles Piana 4 , Jeanne Tomassin-Piana 5 , Maria Paciencia 5 , Eric Lambaudie 6 , Cornel Popovici 2, 7 , Renaud Sabatier 1, 2, 3 , Carole Tarpin 1 , Magali Provansal 1 , Jean-Marc Extra 1 , Francois Eisinger 2, 7 , Hagay Sobol 2, 7 , Patrice Viens 1, 2 , Marc Lopez 2, 3 , Christophe Ginestier 2, 3 , Emmanuelle Charafe-Jauffret 2, 3, 5 , Max Chaffanet 2, 3, # , Daniel Birnbaum 2, 3, # 1 Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France 2 Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France 3 Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France 4 Department of Imaging, Institut Paoli-Calmettes, Marseille, France 5 Department of Biopathology, Institut Paoli-Calmettes, Marseille, France 6 Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France 7 Department of Oncogenetics, Institut Paoli-Calmettes, Marseille, France * both authors equally contributed # both authors equally supervised Correspondence to: Anthony Goncalves, email: goncalvesa@ipc.unicancer.fr Keywords: precision medicine, advanced breast cancer, NGS, CGH, patient-derived xenograft Received: July 10, 2016      Accepted: September 29, 2016      Published: October 18, 2016 ABSTRACT Background: Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population. Results: Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC. Methods: aBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study ( ClinicalTrials.gov , NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX. Conclusions: Precision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases.