Noteware Laura, Broadwater Gloria, Dalal Nicole, Alder Laura, Herndon Ii James E, Floyd Scott, Giles William, Van Swearingen Amanda E D, Anders Carey K, Sammons Sarah
Duke University School of Medicine, Durham, North Carolina, USA.
Biostatistics Shared Resource, Duke Cancer Institute, Durham, North Carolina, USA.
Breast Cancer Res Treat. 2023 Jan;197(2):425-434. doi: 10.1007/s10549-022-06799-7. Epub 2022 Nov 20.
Current systemic therapy guidelines for patients with HER2 + breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2 + BCBrM has never been performed. Our study explores the implications of ECD status on intracranial progression-free survival (iPFS) and overall survival (OS) after first incidence of HER2 + BCBrM and radiation.
A retrospective analysis was performed of 151 patients diagnosed with initial HER2 + BCBrM who received radiation therapy to the central nervous system (CNS) at Duke between 2008 and 2021. The primary endpoint was iPFS defined as the time from first CNS radiation treatment to intracranial progression or death. OS was defined as the time from first CNS radiation or first metastatic disease to death. Systemic staging scans within 30 days of initial BCBrM defined ECD status as progressive, stable/responding or none (isolated brain relapse).
In this cohort, > 70% of patients had controlled ECD with either isolated brain relapse (27%) or stable/responding ECD (44%). OS from initial metastatic disease to death was markedly worse for patients with isolated intracranial relapse (median = 28.4 m) compared to those with progressive or stable/responding ECD (48.8 m and 71.5 m, respectively, p = 0.0028). OS from first CNS radiation to death was significantly worse for patients with progressive ECD (16.9 m) versus stable/responding (36.6 m) or isolated intracranial relapse (28.4 m, p = 0.007). iPFS did not differ statistically based on ECD status. Receipt of systemic therapy after first BCBrM significantly improved iPFS (HR 0.45, 95% CI: 0.25-0.81, p = 0.008) and OS (HR: 0.43 (95% CI: 0.23-0.81); p = 0.001).
OS in patients with HER2 + isolated BCBrM was inferior to those with concurrent progressive or stable/responding ECD. Studies investigating initiation of brain-penetrable HER2-targeted therapies earlier in the disease course of isolated HER2 + intracranial relapse patients are warranted.
HER2阳性乳腺癌脑转移（BCBrM）患者当前的全身治疗指南因颅外疾病（ECD）状态而异。从未对ECD对HER2阳性BCBrM患者预后的影响进行过深入了解。我们的研究探讨了ECD状态对HER2阳性BCBrM首次发病及放疗后颅内无进展生存期（iPFS）和总生存期（OS）的影响。
对2008年至2021年间在杜克大学被诊断为初始HER2阳性BCBrM并接受中枢神经系统（CNS）放射治疗的151例患者进行回顾性分析。主要终点是iPFS，定义为从首次CNS放射治疗到颅内进展或死亡的时间。OS定义为从首次CNS放射治疗或首次转移性疾病到死亡的时间。初始BCBrM后30天内的全身分期扫描将ECD状态定义为进展性、稳定/缓解或无（孤立性脑复发）。
在该队列中，超过70%的患者ECD得到控制，其中孤立性脑复发患者占27%，ECD稳定/缓解患者占44%。与ECD进展或稳定/缓解的患者相比，孤立性颅内复发患者从初始转移性疾病到死亡的OS明显更差（中位数分别为28.4个月、48.8个月和71.5个月，p = 0.0028）。ECD进展的患者从首次CNS放射治疗到死亡的OS明显差于稳定/缓解的患者（16.9个月对36.6个月）或孤立性颅内复发的患者（28.4个月，p = 0.007）。iPFS在不同ECD状态之间无统计学差异。首次BCBrM后接受全身治疗显著改善了iPFS（HR 0.45，95%CI：0.25 - 0.81，p = 0.008）和OS（HR：0.43（95%CI：0.23 - 0.81）；p = 0.001）。
HER2阳性孤立性BCBrM患者的OS低于同时存在进展性或稳定/缓解性ECD的患者。有必要开展研究，在孤立性HER2阳性颅内复发患者的疾病进程中更早地启动可穿透血脑屏障的HER2靶向治疗。
