Ueki Yuko, Horimoto Yoshiya, Harada Kazuharu, Ushiyama Yumiko, Ishizuka Yumiko, Onagi Hiroko, Hayashi Takuo, Saito Tsuyoshi, Kawate Takahiko, Ishikawa Takashi, Watanabe Junichiro, Kutomi Goro
Department of Breast Oncology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of Breast Surgery and Oncology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Breast Cancer. 2025 Jul 20. doi: 10.1007/s12282-025-01745-z.
Estrogen receptor (ER) expression in breast cancer exhibits a widely recognized bimodal distribution, with increasing focus on the biological and clinical characteristics of the low-expression group. However, tumors with intermediate ER expression have been relatively understudied. This study aimed to clarify the clinicopathological and prognostic features of ER-intermediate (ER-int) tumors by comparing them with ER-low tumors.
Tumors were classified into ER-low (1-10%), ER-int (11-70%), and ER-high (71-100%) groups based on immunohistochemistry. We retrospectively analyzed 261 breast cancer patients with ER-low or ER-int tumors who underwent curative surgery. Clinicopathological features and treatment outcomes were compared, and factors influencing distant recurrence-free survival (DRFS) and overall survival (OS) were evaluated using Cox proportional hazard models. For analysis of clinical outcomes, after excluding HER2-positive tumors, an additional cohort of 604 patients with ER-high and HER2-negative tumors was also compared.
ER-int tumors showed lower nuclear grade, higher progesterone receptor expression, and lower Ki67 labeling index compared with ER-low tumors. Pathological stage was independently associated with both DRFS and OS. In addition, ER status was also an independent factor for OS, with ER-int tumors showing significantly better OS than ER-low tumors (P = 0.014).
Our findings, based on comparison with ER-low tumors, suggest that intermediate ER expression may represent a biologically and clinically heterogeneous subgroup within ER-positive breast cancers. Recognition of this heterogeneity could help refine classification and support more individualized treatment strategies.
乳腺癌中雌激素受体（ER）表达呈现出一种广泛认可的双峰分布，人们越来越关注低表达组的生物学和临床特征。然而，ER表达处于中间水平的肿瘤相对研究较少。本研究旨在通过将ER中间型（ER-int）肿瘤与ER低表达肿瘤进行比较，阐明其临床病理特征和预后特征。
基于免疫组织化学将肿瘤分为ER低表达（1%-10%）、ER中间型（11%-70%）和ER高表达（71%-100%）组。我们回顾性分析了261例接受根治性手术的ER低表达或ER中间型肿瘤的乳腺癌患者。比较临床病理特征和治疗结果，并使用Cox比例风险模型评估影响远处无复发生存期（DRFS）和总生存期（OS）的因素。为了分析临床结果，在排除HER2阳性肿瘤后，还比较了另外一组604例ER高表达和HER2阴性肿瘤患者。
与ER低表达肿瘤相比，ER中间型肿瘤显示出更低的核分级、更高的孕激素受体表达和更低的Ki67标记指数。病理分期与DRFS和OS均独立相关。此外，ER状态也是OS的独立因素，ER中间型肿瘤的OS显著优于ER低表达肿瘤（P = 0.014）。
我们基于与ER低表达肿瘤比较的研究结果表明，ER中间型表达可能代表ER阳性乳腺癌中一个生物学和临床异质性的亚组。认识到这种异质性有助于完善分类并支持更个体化的治疗策略。
