Dana-Farber Cancer Institute, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
Cancer Discov. 2022 Sep 2;12(9):2026-2030. doi: 10.1158/2159-8290.CD-22-0703.
The confirmation of the HER2-low paradigm is expected to have a major impact in breast oncology. About half of all breast cancers harbor HER2-low expression, which can be targeted with the anti-HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd), leading to a relevant survival benefit in the metastatic setting. Given this observation, treatment algorithms for both hormone receptor-positive and triple-negative breast cancer are expected to significantly evolve in the next future. Several challenges, however, remain in the interpretation of HER2-low expression related to its biological role, its pathologic diagnosis, and the definition itself of HER2-low. In this article, we recapitulate the current knowledge on HER2-low breast cancer, discussing whether it should be considered a distinct subtype, how it should be implemented in the clinic, and how its definition may evolve in the coming years with the evolution of our clinical and translational knowledge.
HER2 低表达范式的确立有望对乳腺癌治疗产生重大影响。大约一半的乳腺癌存在 HER2 低表达，可使用抗 HER2 抗体药物偶联物曲妥珠单抗 deruxtecan（T-DXd）进行靶向治疗，这可为转移性乳腺癌带来显著的生存获益。鉴于这一观察结果，激素受体阳性和三阴性乳腺癌的治疗方案预计在未来会发生重大变化。然而，在 HER2 低表达的生物学作用、病理诊断及其本身的定义方面，仍存在一些尚未解决的问题。本文回顾了目前关于 HER2 低表达乳腺癌的认识，讨论了其是否应被视为一种独特的亚型，以及如何在临床实践中应用，以及随着我们临床和转化知识的发展，其定义在未来几年可能会如何演变。
