Background Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness. Methods H3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as ‘low’ or ‘high’ expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis. Results The patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066–3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004–3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed ( p = 0.069), reaching statistical significance in younger patients ( p = 0.021). Conclusions H3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.

中文翻译：

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数字成像辅助量化管腔 A/B 样、HER2 阴性、浸润性乳腺癌中的 H3K27me3 免疫表达预测患者存活率和复发风险

背景 乳腺癌 (BC) 是一个主要的健康问题，更好地了解其生物学可能会改善治疗决策和患者预后。Histone3 Lysine27 三甲基化 (H3K27me3) 是一种翻译后组蛋白修饰，通常与基因表达改变相关。在 BC 患者中，较低的 H3K27me3 表达与较差的预后相关。我们使用数字成像软件辅助评估了一组具有长期随访时间的 luminal 样 BC 患者的 H3K27me3 免疫表达，并评估了其与临床相关终点的关联及其临床实用性。方法通过数字成像系统，对 160 例 I-III 期管腔 A/B 样 HER2 阴性侵袭性 BC 的档案组织样本中的 H3K27me3 免疫表达进行评估。使用 Kaplan-Meier 和 Cox 回归进行生存分析。基于由接收者操作特征 (ROC) 曲线分析定义的截止值，病例被分类为“低”或“高”表达。结果 患者队列的中位年龄为 61 岁，中位随访时间为 11.7 年。H3K27me3 低表达（低于 85% 截断值）与复发显着相关，无论是在单变量 (HR = 1.99, 95%CI 1.066–3.724) 还是在调整年级和年龄后的多变量分析中 (HR = 1.89, 95%CI 1.004) –3.559）。观察到 H3K27me3 低表达 BC 死亡风险较高的趋势 (p = 0.069)，在年轻患者中达到统计学显着性 (p = 0.021)。