Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
Clin Cancer Res. 2021 May 15;27(10):2861-2867. doi: 10.1158/1078-0432.CCR-20-4635. Epub 2021 Mar 16.
The prognostic value of estrogen receptor (ER)/progesterone receptor (PgR) expression in ductal carcinoma (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS.
Formalin-fixed paraffin embedded tissues were collected from UK/ANZ DCIS trial participants ( = 755), and ER/PgR expression was evaluated by IHC in 181 cases (with recurrence) matched to 362 controls by treatment arm and age. Assays were scored by the Allred method and by a newly devised clonal method-analyses categorizing multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed.
ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared with DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of IBE [OR 4.99; 95% confidence interval (CI), 2.66-9.36; < 0.0001], but the risk of invasive IBE was not significantly higher (OR 1.72; 95% CI, 0.84-3.53; = 0.14), = 0.03. ER was an independent predictor in multivariate analyses (OR 2.66; 95% CI, 1.53-4.61). PgR status did not add to the prognostic information provided by ER.
ER expression is a strong predictor of ipsilateral recurrence risk in DCIS. ER-positive DCIS with distinct ER-negative clones has a recurrence risk similar to ER-negative DCIS. ER should be routinely assessed in DCIS, and ER scoring should take clonality of expression into account.
雌激素受体（ER）/孕激素受体（PgR）在导管癌（DCIS）中的表达的预后价值尚不清楚。在英国/澳新 DCIS 试验中评估 ER/PgR 表达时，我们观察到了多克隆性，因此，我们研究了 DCIS 中单克隆和多克隆 ER/PgR 表达的预后作用。
从英国/澳新 DCIS 试验参与者（n = 755）中收集福尔马林固定石蜡包埋组织，并通过免疫组化（IHC）在 181 例（有复发）中评估 ER/PgR 表达，这些病例按治疗臂和年龄与 362 例对照相匹配。通过 Allred 法和新设计的克隆法进行分析，将多克隆 DCIS 归类为 ER/PgR 阳性（根据当前实践为标准）和 ER/PgR 阴性（克隆）。
在 70.6%（356/504）的 ER 阳性（ER+）患者中，有 11%（39/356）的 ER 表达为多克隆性。与单克隆 ER 表达的 DCIS 相比，ER 多克隆和 ER 阴性 DCIS 的同侧乳腺事件（IBE）风险也更高。ER 阴性 DCIS（克隆）的 IBE 风险更高[比值比（OR）4.99；95%置信区间（CI），2.66-9.36；<0.0001]，但浸润性 IBE 的风险并没有显著升高（OR 1.72；95%CI，0.84-3.53；=0.14），P=0.03。在多变量分析中，ER 是一个独立的预测因素（OR 2.66；95%CI，1.53-4.61）。
ER 表达是 DCIS 同侧复发风险的有力预测因子。具有明显 ER 阴性克隆的 ER+DCIS 的复发风险与 ER 阴性 DCIS 相似。ER 应常规评估 DCIS，并应考虑表达的克隆性来进行 ER 评分。
