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, p = 0.002; 30 marker panel, p = 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.

中文翻译：

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DNA 甲基化标记可预测三阴性乳腺癌的无复发间隔。

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。对从机构队列中获得的 110 个经过局部区域治疗的样本进行甲基化芯片分析。然后通过 Kaplan-Meier 分析在 IBCSG 试验 VIII 和 IX 的非化疗组中前瞻性收集的 49 个 TNBC 队列中测试发现的标记物组，并在来自联合 IBCSG 试验的 121 个 TNBC 化疗组中通过逻辑回归进行测试和机构存储库。在 IBCSG 研究的非化疗组以及联合机构和 IBCSG 化疗队列中接受化疗的患者中，高甲基化与较短的无复发间隔相关（100 个标记物组，p = 0.002；30 个标记物组） , p = 0.05）。这些位点中 19 号染色体位点富集。总之，我们的高甲基化特征表明复发风险增加，与患者是否接受化疗无关。