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

Anthony Gonçalves (1, 2) , François Bertucci (2, 1) , Arnaud Guille (2, 1) , Severine Garnier (2, 1) , José Adelaide (2, 1) , Nadine Carbuccia (2, 1) , Oliver Cabaud (2, 1) , Pascal Finetti (2, 1) , Serge Brunelle (1) , Gilles Piana (1) , Jeanne Tomassin-Piana (1) , Maria Paciencia (1) , Eric Lambaudie (1) , Cornel Popovici (1, 2) , Renaud Sabatier (2, 1) , Carole Tarpin (1) , Magali Provansal (1) , Jean-Marc Extra (1) , François Eisinger (1, 2) , Hagay Sobol (1, 2) , Patrice Viens (1, 2) , Marc Lopez (1, 2) , Christophe Ginestier (1, 2) , Emmanuelle Charafe-Jauffret (1, 2) , Max Chaffanet (1, 2) , Daniel Birnbaum (1, 2)

1 IPC - Institut Paoli-Calmettes
2 CRCM - Centre de Recherche en Cancérologie de Marseille

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.

Mots clés: CGH; NGS; advanced breast cancer; patient-derived xenograft; precision medicine

Domaines: Cancer

Anthony Gonçalves, François Bertucci, Arnaud Guille, Severine Garnier, José Adelaide, et al.. Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study. Oncotarget, 2016, 7 (48), pp.79428-79441. ⟨10.18632/oncotarget.12714⟩. ⟨hal-03623724⟩