Department of Medical Sciences, University of Turin, Turin, Italy; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
Department of Medical Sciences, University of Turin, Turin, Italy; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
Semin Cancer Biol. 2021 Jul;72:123-135. doi: 10.1016/j.semcancer.2020.02.016. Epub 2020 Feb 26.
The human epidermal growth factor receptor 2 (HER2) is a well-known negative prognostic factor in breast cancer and a target of the monoclonal antibody trastuzumab as well as of other anti-HER2 compounds. Pioneering works on HER2-positive breast cancer in the 90s' launched a new era in clinical research and oncology practice that has reshaped the natural history of this disease. In diagnostic pathology the HER2 status is routinely assessed by using a combination of immunohistochemistry (IHC, to evaluate HER2 protein expression levels) and in situ hybridization (ISH, to assess HER2 gene status). For this purpose, international recommendations have been developed by a consensus of experts in the field, which have changed over the years according to new experimental and clinical data. In this review article we will document the changes that have contributed to a better evaluation of the HER2 status in clinical practice, furthermore we will discuss HER2 heterogeneity defined by IHC and ISH as well as by transcriptomic analysis and we will critically describe the complexity of HER2 equivocal results. Finally, we will introduce the clinical impact of HER2 mutations and we will define the upcoming category of HER2-low breast cancer with respect to emerging clinical data on the efficacy of specific anti-HER2 agents in subgroups of breast carcinomas lacking the classical oncogene addition dictated by HER2 amplification.
人类表皮生长因子受体 2（HER2）是乳腺癌中一个众所周知的不良预后因素，也是曲妥珠单抗等单克隆抗体以及其他抗 HER2 化合物的靶点。90 年代针对 HER2 阳性乳腺癌的开创性研究开启了临床研究和肿瘤学实践的新纪元，改变了这种疾病的自然史。在诊断病理学中，HER2 状态通常通过免疫组织化学（IHC，评估 HER2 蛋白表达水平）和原位杂交（ISH，评估 HER2 基因状态）的组合来评估。为此，该领域的专家达成了共识，制定了国际建议，这些建议根据新的实验和临床数据多年来发生了变化。在这篇综述文章中，我们将记录有助于更好地评估临床实践中 HER2 状态的变化，此外，我们还将讨论由 IHC 和 ISH 以及转录组分析定义的 HER2 异质性，并批判性地描述 HER2 结果不确定的复杂性。最后，我们将介绍 HER2 突变的临床影响，并根据特定抗 HER2 药物在缺乏 HER2 扩增决定的经典致癌基因的乳腺癌亚组中的疗效的新兴临床数据，定义即将出现的 HER2 低水平乳腺癌类别。
