Hu Yan, Jones Daniel, Zhao Weiqiang, Tozbikian Gary, Parwani Anil V, Li Zaibo
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Mod Pathol. 2025 Apr 22;38(8):100783. doi: 10.1016/j.modpat.2025.100783.
The preliminary result of DESTINY-Breast06 trial demonstrated the effectiveness of antibody-drug conjugate in patients with human epidermal growth factor receptor-2 (HER2)-ultralow breast carcinoma (BC), defined by the presence of ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining on HER2 immunohistochemistry. In this study, we investigated the pathologic features and clinical outcomes in patients with HER2-ultralow, HER2-null, and HER2-low expression. The incidence of HER2 ultralow was 17.5% (260/1486). The incidence of other groups is as follows: 7.7% for HER2 null, 56.8% for HER2 low, and 18% for HER2 positive. HER2-ultralow cases showed similarity to HER2-low cases but a significant difference from HER2-null cases, including older age (61.1 vs 57.3 years; P = .0099), fewer grade 3 BCs (18.1% vs 53.9%; P < .0001), triple-negative BCs (16.2% vs 42.6%; P < .0001), estrogen receptor (ER)-negative BCs (16.5% vs 47.8%; P < .0001), and progesterone receptor-negative BCs (26.2% vs 54.8%; P < .0001). When cases were stratified based on ER positivity, these differences between HER2-null and HER2-ultralow groups were confined to ER+ but not ER- cases. There were no discernible differences in response to neoadjuvant chemotherapy (n = 125) among HER2-null, HER2-ultralow, and HER2-low BCs. HER2-null/ER-BCs displayed a lower probability of overall survival than HER2-ultralow and HER2-low/ER-BCs, but no statistically significant difference was observed in disease-free survival among the 3 groups. HER2-ultralow BCs exhibit distinct features that align more closely with HER2-low BCs than HER2-null BCs. These findings contribute to the evolving classification of HER2 expression in BC and may have implications for refining treatment strategies in this subgroup.
DESTINY-Breast06试验的初步结果表明，抗体药物偶联物对人表皮生长因子受体2（HER2）超低表达乳腺癌（BC）患者有效，HER2超低表达定义为HER2免疫组化中浸润癌细胞≤10%呈现不完全且微弱/淡膜染色。在本研究中，我们调查了HER2超低表达、HER2阴性和HER2低表达患者的病理特征及临床结局。HER2超低表达的发生率为17.5%（260/1486）。其他组的发生率如下：HER2阴性为7.7%，HER2低表达为56.8%，HER2阳性为18%。HER2超低表达病例与HER2低表达病例表现出相似性，但与HER2阴性病例有显著差异，包括年龄较大（61.1岁对57.3岁；P = 0.0099）、3级BC较少（18.1%对53.9%；P < 0.0001）、三阴性BC较少（16.2%对42.6%；P < 0.0001）、雌激素受体（ER）阴性BC较少（16.5%对47.8%；P < 0.0001）以及孕激素受体阴性BC较少（26.2%对54.8%；P < 0.0001）。当根据ER阳性进行分层时，HER2阴性和HER2超低表达组之间的这些差异仅限于ER + 病例，而ER - 病例则无差异。HER2阴性、HER2超低表达和HER2低表达的BC对新辅助化疗（n = 125）的反应没有明显差异。HER2阴性/ER - BC的总生存概率低于HER2超低表达和HER2低表达/ER - BC，但三组之间的无病生存没有观察到统计学上的显著差异。HER2超低表达的BC表现出与HER2低表达BC比HER2阴性BC更密切相关的独特特征。这些发现有助于完善BC中HER2表达的分类，可能对优化该亚组的治疗策略有影响。
