Visvanathan Kala, Cope Leslie, Fackler Mary Jo, Considine Michael, Sokoll Lori, Carey Lisa A, Forero-Torres Andres, Ingle James N, Lin Nancy U, Nanda Rita, Storniolo Anna Maria, Tulac Suzana, Venkatesan Neesha, Wu Natalie C, Marla Sudhakar, Campbell Scott, Bates Michael, Umbricht Christopher B, Wolff Antonio C, Sukumar Saraswati
Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Cancer Res. 2023 Feb 16;29(4):784-790. doi: 10.1158/1078-0432.CCR-22-2128.
We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC.
The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC.
At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20-3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77-11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29-5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment.
The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.
我们之前证明，循环甲基化DNA水平升高与转移性乳腺癌（MBC）女性患者随后的疾病进展相关。在本研究中，我们评估了一种使用GeneXpert cartridge系统的新型液体活检-乳腺癌甲基化（LBx-BCM）原型检测方法在MBC疾病进展早期评估中的临床应用价值。
在一项前瞻性生物标志物研究TBCRC 005中，使用从144例MBC患者基线、第4周和第8周采集的血浆，对9标志物LBx-BCM原型检测方法进行评估。
在第4周时，与低累积甲基化（CM）的MBC患者相比，高CM患者的中位无进展生存期（PFS）显著缩短（2.88个月对6.60个月，P = 0.001），总生存期（OS）也显著缩短（14.52个月对22.44个月，P = 0.005）。在多变量模型中，高CM与低CM相比也与较短的PFS相关（风险比[HR]，1.90；95%置信区间[CI]，1.20 - 3.01；P = 0.006）。从基线到第4周CM的变化（比值比[OR]，4.60；95% CI，1.77 - 11.93；P = 0.002）以及第4周时的高CM水平（OR，2.78；95% CI，1.29 - 5.99；P = 0.009）与首次重新分期时的疾病进展相关。基于第4周循环CM水平建立了一个强大的风险模型，以预测在开始新治疗后最早3个月的疾病进展。
自动化的LBx-BCM原型检测方法是一种有前景的临床工具，可用于在接受常规护理的MBC女性患者开始治疗后一个月检测疾病进展。下一步是验证其在特定治疗中的临床应用价值。
