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

Edité par CCSD ; Impact journals -

International audience. 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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