Detection of MRD in TNBC Through Multi-Platform Molecular Biomarker Analysis

我们研究计划的首要目标是了解三阴性分子的异质性。 乳腺癌(TNBC)，以识别和验证既可预测预后又可预测的生物标记物， 并最终基于每个患者的肿瘤生物学来优化治疗。朝向这个方向 结束，我们最近获得了资金，用于进行一项由研究人员发起的预期临床试验，该试验名为 三阴性乳腺癌(AIM-TNBC)微小残留病变的辅助强化 对TNBC术后残留病变患者强化辅助系统治疗的评价 新辅助系统疗法。在Natera，Inc.的行业支持下，我们将使用个性化循环 肿瘤DNA(CtDNA)分析，以确定患者的微小残留病，然后随机进行这些 高危患者接受标准护理与强化辅助治疗。我们对这次KIPM的具体目标 COBRE的应用有：(1)评估循环肿瘤细胞(CTCs)和非编码RNA (NcRNAs)在血浆来源的胞外小泡(EVS)中作为最低限度的额外生物标志物 在我们的前瞻性AIM-TNBC试验中确定高危MRD特征的残留疾病和(2) 了解分子生物标记物信息如何影响TNBC患者对 个体复发风险和接受辅助治疗的意愿。这项工作最终会改进的 我们有能力对TNBC患者进行风险分层，并确定哪些人可能从强化的 辅助性全身治疗。这一目标与KIPM Cobre提供精确度的使命一致 医学：它考虑疾病分子组成中的个体变异性，目的是 针对每个患者独特的生物特点进行量身定制的治疗。

The overarching goal of our research program is to understand the molecular heterogeneity of triple-negative breast cancer (TNBC), to identify and validate biomarkers that are both prognostic and predictive, and ultimately to optimize treatment for each patient based on the biology of her/his tumor. Towards this end, we have recently received funding to conduct a prospective investigator-initiated clinical trial entitled Adjuvant Intensification for Minimal Residual Disease in Triple-Negative Breast Cancer (AIM-TNBC) that is evaluating intensification of adjuvant systemic therapy in TNBC patients with residual disease after neoadjuvant systemic therapy. With industry support from Natera, Inc., we will use personalized circulating tumor DNA (ctDNA) analysis to identify patients with minimal residual disease and then randomize these high-risk patients to standard-of-care versus intensified adjuvant therapy. Our specific aims for this KIPM COBRE application are (1) to evaluate circulating tumor cells (CTCs) and non-coding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EVs) as additional biomarkers of minimal residual disease to define a high-risk MRD signature in our prospective AIM-TNBC trial and (2) to understand how molecular biomarker information influences TNBC patients’ perception of individual relapse risk and willingness to accept adjuvant therapy. This work will ultimately improve our ability to risk-stratify TNBC patients and identify those who are likely to benefit from intensification of adjuvant systemic therapy. This goal is aligned with the KIPM COBRE’s mission of providing precision medicine in that it considers individual variability in the molecular composition of one’s disease and aims to tailor treatment towards each patient’s unique biology.