Yi Zongbi, Feng Kaixiang, Lv Dan, Guan Yanfang, Shao Youcheng, Ma Fei, Xu Binghe
Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Signal Transduct Target Ther. 2024 Dec 9;9(1):345. doi: 10.1038/s41392-024-02047-0.
The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance. In this study, we retrospectively analyzed 1071 metastatic breast cancer (MBC) patients and the circulating tumor DNA (ctDNA) to investigate clinicopathological and genetic alterations of HER2-low MBC patients. The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials (NCT03412383, NCT01917279) and a retrospective study. Our findings suggest TP53, PIK3CA, and ESR1 are frequently mutated genes in HER2-low MBC. Compared to the HER2-0 group, mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations. Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group. Notably, we did not find any statistically significant disparity in the response to chemotherapy, endocrine therapy, or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients. Interestingly, within the subgroup of individuals with metabolic pathway-related gene mutations, we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group. Additionally, dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles, exhibited prolonged survival. Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.
大量HER2低表达乳腺癌患者需要进一步研究以提供更强的临床指导。在本研究中，我们回顾性分析了1071例转移性乳腺癌（MBC）患者及循环肿瘤DNA（ctDNA），以研究HER2低表达MBC患者的临床病理和基因改变。在两项前瞻性临床试验（NCT03412383、NCT01917279）和一项回顾性研究中探讨了HER2低表达状态对不同治疗方式的影响。我们的研究结果表明，TP53、PIK3CA和ESR1是HER2低表达MBC中常见的突变基因。与HER2-0组相比，HER2低表达组中观察到的突变与代谢途径改变的相关性更强。此外，在接受吡咯替尼治疗的ERBB2突变患者中，HER2低表达组与HER2-0组相比可能预后更好。值得注意的是，我们未发现HER2-0和HER2低表达乳腺癌患者在化疗、内分泌治疗或CDK4/6抑制剂治疗反应上存在任何统计学显著差异。有趣的是，在代谢途径相关基因突变的亚组中，我们发现HER2低表达组与HER2-0组相比对这些治疗表现出更有利的反应。此外，动态分析显示，在最初两个治疗周期后分子肿瘤负荷指数降低或实现ctDNA早期清除的HER2低表达MBC患者生存期延长。此外，我们将HER2低表达MBC分为三个簇，为后续更精准的治疗提供参考。我们的研究为HER2低表达MBC的生物学特性提供了有价值的见解，并可能为个性化治疗策略提供参考。
