Fackler Mary Jo, Cho Soonweng, Cope Leslie, Gabrielson Edward, Visvanathan Kala, Wilsbach Kathleen, Meir-Levi Danielle, Lynch Charles F, Marks Jeffrey, Geradts Joseph, Regan Meredith M, Viale Giuseppe, Wolff Antonio C, Sukumar Saraswati, Umbricht Christopher B
1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
2Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
NPJ Breast Cancer. 2020 Jan 31;6:3. doi: 10.1038/s41523-020-0145-3. eCollection 2020.
We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from institutional cohorts. Discovered marker sets were then tested by Kaplan-Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no-chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and institutional repositories. High methylation was associated with shorter recurrence-free interval in the no-chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined institutional and IBCSG chemotherapy cohorts (100 marker panel, = 0.002; 30 marker panel, = 0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.
我们缺乏对三阴性乳腺癌（TNBC）进行风险分层的工具。我们的目标是开发分子工具来预测疾病复发。对从机构队列中获取的110例接受局部区域治疗的样本进行了甲基化阵列分析。然后，在一项前瞻性收集的TNBC队列（来自国际乳腺癌研究组（IBCSG）试验VIII和IX无化疗组的49个样本）中，通过Kaplan-Meier分析对发现的标志物集进行测试，并在一项来自IBCSG试验和机构储存库组合的121例接受化疗的TNBC患者队列中，通过逻辑回归进行测试。在IBCSG研究的无化疗组以及机构与IBCSG化疗组合队列中接受化疗的患者中，高甲基化与较短的无复发生存期相关（100个标志物组，P = 0.002；30个标志物组，P = 0.05）。这些位点中19号染色体区域富集。总之，我们的高甲基化特征表明，无论患者是否接受化疗，复发风险均会增加。
