Molinelli Chiara, Jacobs Flavia, Marchiò Caterina, Pitto Francesca, Cosso Maurizio, Spinaci Stefano, de Azambuja Evandro, Schettini Francesco, Agostinetto Elisa, Lambertini Matteo
Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium.
Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
Breast Care (Basel). 2022 Dec;17(6):533-545. doi: 10.1159/000527391. Epub 2022 Oct 6.
Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies.
The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs.
Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.
乳腺癌传统上根据激素受体和HER2状态分为三种临床亚型（即管腔样、HER2阳性和三阴性）。每种亚型都有独特的临床病理和分子特征，需要进行针对性治疗。最近的研究工作集中在一种新的分类上，即确定所谓的“HER2低表达”类别，包括以HER2表达水平低为特征的肿瘤（免疫组织化学评分1+或2+且无原位杂交扩增）。新出现的证据表明，HER2低表达肿瘤患者可从特定的抗HER2治疗中获益。这代表了乳腺癌肿瘤学领域的一项重大进展，更多比例的乳腺癌患者最终可从新的有效靶向治疗策略中获益。
抗体药物偶联物曲妥珠单抗德卢替康已在HER2低表达乳腺癌患者中显示出令人印象深刻的疗效，目前还有其他几种药物正在该患者亚组中进行研究。需要进一步研究以解决该领域存在的未决问题，包括对HER2低表达状态进行适当的病理评估、阐明其预后意义以及全球范围内获得新批准药物的途径。
我们的综述旨在总结关于HER2低表达乳腺癌的现有证据，阐述当前正在解决的挑战以及这个令人兴奋的新领域的未来前景。
