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Abstract：
BACKGROUND: Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD.
METHODS: Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS.
RESULTS: 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD.
CONCLUSIONS: Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
METHODS: Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS.
RESULTS: 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD.
CONCLUSIONS: Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
摘要：
背景：乳腺癌相关的软脑膜疾病（BC-LMD）是5-8％的乳腺癌（BC）患者的明确诊断。我们对2011年至2020年在Moffitt癌症中心诊断的BC-LMD患者进行了回顾性研究，以确定BC-LMD的发病率变化。与BCCNS转移进展为BC-LMD相关的因素，以及与BC-LMD患者OS相关的因素。
方法：确定患有BC和脑/脊柱转移疾病的患者。对于那些最终开发BC-LMD的人来说，我们用Kaplan-Meier存活曲线,对数秩检验，单变量,和多变量Cox比例风险回归模型来确定影响从CNS转移到BC-LMD和OS的时间的因素。
结果：128例BC-LMD。与2011-2015年相比，2016年至2020年期间，BC-LMD占总BC患者的比例更高。与三阴性乳腺癌（TNBC）患者相比，HR或HER2BC患者在CNS转移和LMD之间经历了更长的时间。全身治疗和全脑放射治疗（WBRT）与所有患者的LMD进展延长有关。HR+BC患者的激素治疗与LMD进展的延迟BC-CNS转移相关。拉帕替尼治疗与HER2+BC患者LMD进展延迟相关。与HR+和HER2+BC-LMD患者相比，TNBC-LMD患者的OS较短。全身治疗,鞘内（IT）治疗，WBRT与所有患者的生存期延长相关。拉帕替尼和曲妥珠单抗治疗与HER2+BC-LMD患者OS改善相关。
结论：BC-LMD的增加为临床试验提供了治疗挑战和机遇。测试拉帕替尼和/或类似酪氨酸激酶抑制剂的前瞻性试验，IT疗法,迫切需要联合治疗。
方法：确定患有BC和脑/脊柱转移疾病的患者。对于那些最终开发BC-LMD的人来说，我们用Kaplan-Meier存活曲线,对数秩检验，单变量,和多变量Cox比例风险回归模型来确定影响从CNS转移到BC-LMD和OS的时间的因素。
结果：128例BC-LMD。与2011-2015年相比，2016年至2020年期间，BC-LMD占总BC患者的比例更高。与三阴性乳腺癌（TNBC）患者相比，HR或HER2BC患者在CNS转移和LMD之间经历了更长的时间。全身治疗和全脑放射治疗（WBRT）与所有患者的LMD进展延长有关。HR+BC患者的激素治疗与LMD进展的延迟BC-CNS转移相关。拉帕替尼治疗与HER2+BC患者LMD进展延迟相关。与HR+和HER2+BC-LMD患者相比，TNBC-LMD患者的OS较短。全身治疗,鞘内（IT）治疗，WBRT与所有患者的生存期延长相关。拉帕替尼和曲妥珠单抗治疗与HER2+BC-LMD患者OS改善相关。
结论：BC-LMD的增加为临床试验提供了治疗挑战和机遇。测试拉帕替尼和/或类似酪氨酸激酶抑制剂的前瞻性试验，IT疗法,迫切需要联合治疗。
