ctDNA引导下曲妥珠单抗-德鲁克斯替康联合焦替尼精准治疗HER2阳性乳腺癌症脑转移：一例报告
ctDNA-guided precision therapy with trastuzumab deruxtecan plus pyrotinib in HER2-positive breast cancer brain metastases: a case report.
摘要(中文译文)
脑转移发生于30%-55%的HER2阳性转移性乳腺癌患者中，构成重大的治疗挑战。循环肿瘤DNA（ctDNA）监测已成为一种可能有助于更早进行疾病活动分子检测的工具。我们报告一例35岁女性，妊娠期间诊断为HER2阳性转移性乳腺癌，经标准治疗后达到病理学完全缓解。鉴于其年轻年龄、IV期疾病及非典型的妊娠相关表现，诊断时进行了基线全面基因组分析。连续ctDNA监测在影像学证据显示脑转移前约三个月检测到阳性。基因组分析揭示了可能促进疾病生物学演变的新发变异，包括MET扩增和HER2 V777L突变。基于ctDNA动态变化和分子谱，采用曲妥珠单抗德鲁替康联合吡咯替尼治疗，在17个月的随访中与颅内疾病控制相关。药物性肝毒性通过剂量调整和支持治疗得到管理，未中断治疗。本病例说明了将ctDNA监测纳入治疗决策的可行性，并提供了关于联合治疗管理HER2阳性脑转移的假设生成性观察。此处观察到的分子学与影像学发现之间的时间关系提示了更早检测疾病活动的潜在价值，尽管这种提前时间是否转化为改善的临床结局尚需前瞻性验证。这些发现支持对该方法进行前瞻性评估，包括正在进行的探究该治疗策略的TROPHY试验。
Abstract
Brain metastases occur in 30-55% of patients with HER2-positive metastatic breast cancer, presenting significant therapeutic challenges. Circulating tumor DNA (ctDNA) monitoring has emerged as a potentially useful tool for earlier molecular detection of disease activity. We report a 35-year-old woman with HER2-positive metastatic breast cancer diagnosed during pregnancy who achieved pathological complete response after standard therapy. Given her young age, stage IV disease, and atypical pregnancy-associated presentation, baseline comprehensive genomic profiling was performed at diagnosis. Serial ctDNA monitoring detected positivity approximately three months prior to radiologic evidence of brain metastases. Genomic profiling revealed newly emergent alterations potentially contributory to evolving disease biology, including MET amplification and HER2 V777L mutation. Treatment with trastuzumab deruxtecan plus pyrotinib, informed by ctDNA dynamics and the molecular profile, was associated with intracranial disease control over 17 months of follow-up. Drug-induced hepatotoxicity was managed through dose modifications and supportive care without treatment interruption. This case illustrates the feasibility of incorporating ctDNA monitoring into treatment decisions and provides a hypothesis-generating observation regarding combination therapy in managing HER2-positive brain metastases. The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.
如何引用
AMA
Danyang Zhou, Ying Wu, Siyu Guo, Ping Li, Guangxin Li, Mengqi Yang, et al. ctDNA-guided precision therapy with trastuzumab deruxtecan plus pyrotinib in HER2-positive breast cancer brain metastases: a case report.. Frontiers in oncology. 2026; doi:10.3389/fonc.2026.1826447.
APA
Danyang Zhou, Ying Wu, Siyu Guo, Ping Li, Guangxin Li, Mengqi Yang, et al (2026). ctDNA-guided precision therapy with trastuzumab deruxtecan plus pyrotinib in HER2-positive breast cancer brain metastases: a case report.. Frontiers in oncology. https://doi.org/10.3389/fonc.2026.1826447
GB/T 7714
Danyang Zhou, Ying Wu, Siyu Guo, Ping Li, Guangxin Li, Mengqi Yang, et al. ctDNA-guided precision therapy with trastuzumab deruxtecan plus pyrotinib in HER2-positive breast cancer brain metastases: a case report.[J]. Frontiers in oncology, 2026 doi:10.3389/fonc.2026.1826447.
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