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Abstract：
BACKGROUND: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient\'s tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients.
METHODS: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model.
CONCLUSIONS: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation.
BACKGROUND: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.
METHODS: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model.
CONCLUSIONS: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation.
BACKGROUND: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.
摘要：
背景：三阴性乳腺癌（TNBC）约占所有乳腺癌的15％，并且与较短的中位生存期相关，主要是由于局部晚期肿瘤和高转移风险。目前TNBC的新辅助治疗包括免疫检查点阻断剂和化疗(chemo-ICB)的方案。尽管经常使用这种组合治疗TNBC，观察到中等结果,其在TNBC中的临床获益仍难以预测.患者来源的肿瘤类器官(PDTO)是从患者的肿瘤样品获得的3D体外细胞结构。越来越多的证据表明，这些模型可以预测其来源的肿瘤的反应。因此,PDTO可用作预测TNBC患者中的化学-ICB功效的工具。
方法：TRIPLEX研究是一项单中心观察性研究，旨在研究从TNBC产生PDTO的可行性，并评估其预测临床反应的能力。PDTO将在活检分离并嵌入细胞外基质后获得。PDTO将在补充有生长因子和信号通路抑制剂的培养基中培养。将对已建立的PDTO系进行分子和组织学分析，以验证它们与原始肿瘤的表型接近度。将使用与从患者血液样品收集的自体免疫细胞的共培养来评估PDTO对chemo-ICB的反应。最后将PDTO反应与患者的反应进行比较，以评估模型的预测潜力。
结论：本研究将评估使用PDTO作为评估TNBC患者对治疗反应的预测工具的可行性。如果PDTO能够在临床相关的时间范围内忠实地预测患者的反应，可以设计一项前瞻性临床试验,使用PDTO指导临床决策.这项研究还将允许建立TNBCPDTO的活生物库，可用于未来的创新策略评估。
背景：临床试验（版本1.2）已于2021年12月30日由当地研究伦理委员会验证，并于2022年6月3日在ClinicalTrials.gov注册，标识符为NCT05404321，版本1.2。
方法：TRIPLEX研究是一项单中心观察性研究，旨在研究从TNBC产生PDTO的可行性，并评估其预测临床反应的能力。PDTO将在活检分离并嵌入细胞外基质后获得。PDTO将在补充有生长因子和信号通路抑制剂的培养基中培养。将对已建立的PDTO系进行分子和组织学分析，以验证它们与原始肿瘤的表型接近度。将使用与从患者血液样品收集的自体免疫细胞的共培养来评估PDTO对chemo-ICB的反应。最后将PDTO反应与患者的反应进行比较，以评估模型的预测潜力。
结论：本研究将评估使用PDTO作为评估TNBC患者对治疗反应的预测工具的可行性。如果PDTO能够在临床相关的时间范围内忠实地预测患者的反应，可以设计一项前瞻性临床试验,使用PDTO指导临床决策.这项研究还将允许建立TNBCPDTO的活生物库，可用于未来的创新策略评估。
背景：临床试验（版本1.2）已于2021年12月30日由当地研究伦理委员会验证，并于2022年6月3日在ClinicalTrials.gov注册，标识符为NCT05404321，版本1.2。
