BACKGROUND In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice. METHODS We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies. RESULTS A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study. CONCLUSION This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.

中文翻译：

---

激素受体乳腺癌的预后 DNA 甲基化标记：系统评价。


背景技术在激素受体阳性乳腺癌患者中，区分复发风险低和高的患者是一个持续的挑战。在当前实践中，预后临床参数用于风险预测。 DNA 甲基化标记已被证明对多种癌症类型具有额外的预后价值。文献中已发表了许多乳腺癌预后 DNA 甲基化标记物。然而，迄今为止，这些标记物均未用于临床实践。方法 我们对 PubMed 和 EMBASE 进行了系统回顾，以评估已发表的激素受体阳性乳腺癌 DNA 甲基化标记物的证据数量和水平。为了全面了解纳入研究的报告质量，所有研究均根据作为预后生物标志物研究报告指南而制定的 REMARK 标准进行评分。结果 总共确定了 74 项研究，报告了 87 种不同的 DNA 甲基化标记。备注标准的评估显示研究报告质量存在差异。在多个独立群体中研究了十八个单一标记和一个标记组。标记物 RASSF1、BRCA、PITX2、CDH1、RARB、PCDH10 和 PGR 以及标记物组 GSTP1、RASSF1 和 RARB 的高甲基化显示出与不良疾病结果存在统计学显着相关性，这一点至少在另一项独立研究中得到证实。结论 本系统综述概述了已发表的激素受体阳性乳腺癌预后 DNA 甲基化标记物，并确定了八种经过独立验证的标记物。 对纳入研究的报告质量的分析表明，该主题的未来研究将受益于标准化报告指南。