目的:脑膜疾病(LMD)是转移性乳腺癌(MBC)的破坏性并发症。更好地了解风险因素至关重要,自然史,和治疗结果,包括现代队列中的患者。
方法:在这项单中心回顾性队列研究中,我们确定了从2000年到2024年接受治疗的MBC和LMD患者,并提取了关键的临床,治疗,和生存数据。
结果:我们确定了111例MBC和LMD患者,包括以下亚型的患者:HR+/HER2-(n=53,47.7%),HER2+(n=30,27.0%),三阴性乳腺癌(TNBC;n=28,25.2%)。从MBC诊断到LMD的中位时间为16.4个月(范围0-101.3个月)。确诊LMD后,大多数患者接受了全身治疗(n=66,59.5%)和/或中枢神经系统(CNS)定向治疗(n=94,84.7%),包括鞘内治疗(n=42,37.8%)和/或CNS定向放射治疗(n=70,63.1%).在所有患者中,从诊断LMD到死亡的中位总生存期(OS)为4.1个月(范围0.1-78.1个月),且因亚型而异,HR+/HER2-或HER2+MBC患者的寿命比TNBC患者长(分别为4.2和6.8个月与2.0个月,p<0.01,HR2.15,95%CI1.36-3.39)。接受中枢神经系统导向治疗的患者比未接受治疗的患者寿命更长(4.2vs.1.3,p=0.02HR0.54,0.32-0.91)。2015年至2024年诊断为LMD的患者比2000年至2014年诊断为LMD的患者寿命更长(6.4vs.2.9个月,p=0.04,HR0.67,95%CI0.46-0.99)。在多变量分析中,从LMD到死亡,TNBC与OS较短相关(p=0.004,HR2.03,95%CI1.25-3.30).
结论:这是最大的MBC和LMD患者系列之一。2015年至2024年诊断为LMD的患者比2000年至2014年诊断的患者寿命更长,尽管总体中位OS较短。TNBC和LMD患者的OS特别短。LMD的新治疗策略仍然是未满足临床需求的领域。
OBJECTIVE: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort.
METHODS: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data.
RESULTS: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30).
CONCLUSIONS: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.