Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
Breast Cancer Res Treat. 2013 Jun;139(3):741-50. doi: 10.1007/s10549-013-2570-6. Epub 2013 May 31.
Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.
乳腺癌是一种高度异质性的恶性肿瘤。三阴性乳腺癌（TNBC）和人表皮生长因子受体 2（HER2）乳腺癌亚型侵袭性强，预后差。TNBC 的治疗靶点仍未确定，许多 HER2 亚型患者在长期治疗后会产生耐药性。本研究旨在评估 HER3 表达在浸润性乳腺癌中的预后意义。我们建立了匹配的组织微阵列（TMA）块和 950 例浸润性乳腺癌的临床数据，这些患者具有长期的临床随访数据（中位数为 109.7 个月）。使用 TMA，我们通过免疫组织化学对 ER、PR、HER2、EGFR 和 HER3 的表达进行了特征描述。根据激素受体（HR）和 HER2 的表达，将每个病例分为四种基于 IHC 的亚型之一。通过亚型分析了 950 例患者的临床病理特征和生存情况。在 TNBC 亚型中，HER3(+)组的无病生存率（DFS，P=0.010）和总生存率（OS，P=0.015）均比 HER3(-)组差。在 HER2 亚型中，HER3(+)组的 DFS（P=0.022）和 OS（P=0.077）也比 HER3(-)组差。然而，在 HR 阳性乳腺癌患者中没有差异。HER3 表达与 TNBC 和 HER2 亚型的 DFS 不良相关，与 TNBC 亚型的 OS 不良相关。HER3 过表达是激素受体阴性乳腺癌的重要预后标志物，需要进一步研究以阐明 HER-3 靶向治疗的作用。
