Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study
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Anthony Gonçalves1,2,*, François Bertucci1,2,3,*, Arnaud Guille2,3, Severine Garnier2,3, José Adelaide2,3, Nadine Carbuccia2,3, Oliver Cabaud2,3, Pascal Finetti2,3, Serge Brunelle4, Gilles Piana4, Jeanne Tomassin-Piana5, Maria Paciencia5, Eric Lambaudie6, Cornel Popovici2,7, Renaud Sabatier1,2,3, Carole Tarpin1, Magali Provansal1, Jean-Marc Extra1, François Eisinger2,7, Hagay Sobol2,7, Patrice Viens1,2, Marc Lopez2,3, Christophe Ginestier2,3, Emmanuelle Charafe-Jauffret2,3,5, Max Chaffanet2,3,#, Daniel Birnbaum2,3,#
1Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
2Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France
3Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France
4Department of Imaging, Institut Paoli-Calmettes, Marseille, France
5Department of Biopathology, Institut Paoli-Calmettes, Marseille, France
6Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France
7Department of Oncogenetics, Institut Paoli-Calmettes, Marseille, France
*both authors equally contributed
#both authors equally supervised
Anthony Gonçalves, email: firstname.lastname@example.org
Keywords: precision medicine, advanced breast cancer, NGS, CGH, patient-derived xenograft
Received: July 10, 2016 Accepted: September 29, 2016 Published: October 18, 2016
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.
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