Debeb Bisrat G, Gong Yun, Atkinson Rachel L, Sneige Nour, Huo Lei, Gonzalez-Angulo Ana Maria, Hung Mien-Chie, Valero Vicente, Ueno Naoto T, Woodward Wendy A
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
J Exp Clin Cancer Res. 2014 Jul 23;33(1):58. doi: 10.1186/s13046-014-0058-9.
Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group proteins, has been shown to promote cancer progression and breast cancer stem cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer. In this retrospective study, we examined the clinical role of EZH2 in locoregional recurrence (LRR) of IBC patients treated with radiation.
62 IBC patients who received radiation (7 pre-operative, 55 post-operative) and had adequate follow up to assess LRR were the subject of this study. Positive EZH2 status was defined as nuclear immunohistochemical staining in at least 10% of invasive cancer cells. Association of EZH2 expression with clinicopathologic features were evaluated using the Chi-square statistic and actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method.
The median follow-up for this cohort was 33.7 months, and the 5-year overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of 16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year locoregional free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs. 59.1%; P = 0.01). Positive EZH2 expression was associated significantly with negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive. In multivariate analysis, only triple negative status remained an independent predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 - 14.49, P < 0.0001).
EZH2 correlates with locoregional recurrence in IBC patients who received radiation treatment. EZH2 expression status may be used in addition to receptor status to identify a subset of patients with IBC who recur locally in spite of radiation and may benefit from enrollment in clinical trials testing radiosensitizers.
zeste 同源物增强子 2（EZH2）是多梳蛋白家族的成员之一，已被证明可促进癌症进展和乳腺癌干细胞（CSC）的扩增。乳腺癌干细胞与炎性乳腺癌（IBC）对放疗的抗性相关，IBC 是一种罕见但侵袭性强的乳腺癌亚型。在这项回顾性研究中，我们研究了 EZH2 在接受放疗的 IBC 患者局部区域复发（LRR）中的临床作用。
本研究纳入 62 例接受放疗的 IBC 患者（7 例术前放疗，55 例术后放疗），且有足够的随访时间以评估 LRR。EZH2 阳性状态定义为至少 10%的浸润癌细胞呈细胞核免疫组化染色阳性。采用卡方检验评估 EZH2 表达与临床病理特征的相关性，并使用 Kaplan-Meier 方法确定精算局部区域无复发生存率（LRFS）。
该队列的中位随访时间为 33.7 个月，5 年总体 LRFS 率为 69%。62 例患者中，16 例（25.8%）发生 LRR，16 例 LRR 中有 15 例发生在 EZH2 表达阳性的病例中。单因素分析表明，EZH2 阳性的 IBC 患者 5 年局部区域无复发生存率（LRFS）显著低于 EZH2 阴性的 IBC 患者（93.3%对 59.1%；P = 0.01）。EZH2 阳性表达与雌激素受体（ER）阴性状态显著相关（ER-中为 97.1%，ER+中为 48.1%；P < 0.0001）以及三阴性受体状态（P = 0.0001），所有三阴性肿瘤均为 EZH2 阳性。多因素分析中，只有三阴性状态仍然是 LRFS 较差的独立预测因素（风险比 5.64，95%置信区间 2.19 - 14.49，P < 0.0001）。
EZH2 与接受放疗的 IBC 患者的局部区域复发相关。除受体状态外，EZH2 表达状态可用于识别一部分尽管接受了放疗仍局部复发的 IBC 患者，这些患者可能从参加测试放疗增敏剂的临床试验中获益。
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