Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study.
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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DOI：
10.18632/oncotarget.12714
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发表时间：
2016-11-29
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影响因子：
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通讯作者：
Birnbaum D
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作者：
Gonçalves A;Bertucci F;Guille A;Garnier S;Adelaide J;Carbuccia N;Cabaud O;Finetti P;Brunelle S;Piana G;Tomassin-Piana J;Paciencia M;Lambaudie E;Popovici C;Sabatier R;Tarpin C;Provansal M;Extra JM;Eisinger F;Sobol H;Viens P;Lopez M;Ginestier C;Charafe-Jauffret E;Chaffanet M;Birnbaum D
基于基因组学的肿瘤分析对晚期乳腺癌 (aBC) 的常规可行性和临床影响仍有待确定。我们进行了一项试点研究，以评估是否可以在单一中心前瞻性地对 aBC 患者实施精准医疗，并检查是否可以在该人群中获得患者来源的肿瘤异种移植物 (PDX)。包括 34 名 aBC 患者。在 28 名患者 (82%) 中找到了可行的目标。通过临床试验 (n=15) 和/或使用已经注册的药物 (n=21)，可以向 22 名患者 (64%) 提出靶向治疗。 10 名患者（29%）最终接受了靶向治疗，其中 2 名患者获得了临床获益。在 22 名接受小鼠移植的患者中，10 名患者异种移植成功（45%），其中大部分为三阴性 aBC。可进行肿瘤活检的 aBC 患者前瞻性地在 Paoli-Calmettes 研究所纳入 BC-BIO 研究（ClinicalTrials.gov，NCT01521676）。通过全基因组阵列比较基因组杂交 (aCGH) 和 365 个候选癌症基因的靶向下一代测序 (NGS) 建立了基因组分析。对于一部分患者，将新鲜肿瘤样本原位植入 NSG 小鼠的人源化透明脂肪垫中，以建立 PDX。精准医学可以在临床实践的背景下在单一中心实施，并可能允许对大约 30% 的 aBC 患者进行基因组驱动的治疗。在相当一部分病例中可以获得 PDX。
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. 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. 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. 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.