Wallace Gerald, Kundalia Ronak, Cao Biwei, Kim Youngchul, Smalley Inna, Forsyth Peter, Soyano Aixa, Pina Yolanda
H. Lee Moffitt Cancer Center and Research Institute.
Res Sq. 2023 Jun 8:rs.3.rs-2981094. doi: 10.21203/rs.3.rs-2981094/v1.
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 (MCC) from 2011-2020, to determine the changing incidence of BC-LMD, which factors impact progression of BC CNS metastasis to BC-LMD, and which factors affect OS for patients with BC-LMD.
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.
128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016-2020 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) prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC delayed BC-CNS metastasis to LMD progression. Lapatinib 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 prolonged survival for all patients. Lapatinib and trastuzumab improved OS in patients with HER2 + BC-LMD.
Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
乳腺癌相关软脑膜疾病(BC-LMD)是5%-8%乳腺癌(BC)患者的严重诊断结果。我们对2011年至2020年在莫菲特癌症中心(MCC)诊断出的BC-LMD患者进行了回顾性研究,以确定BC-LMD发病率的变化、哪些因素影响BC中枢神经系统转移进展为BC-LMD,以及哪些因素影响BC-LMD患者的总生存期(OS)。
确定患有BC和脑/脊髓转移性疾病的患者。对于最终发展为BC-LMD的患者,我们使用Kaplan-Meier生存曲线、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中枢神经系统转移到BC-LMD的时间以及OS的因素。
共确定了128例BC-LMD病例。与2011年至2015年相比,2016年至2020年期间BC-LMD占BC患者总数的比例更高。激素受体(HR)阳性或人表皮生长因子受体2(HER2)阳性的BC患者在中枢神经系统转移和LMD之间经历的时间比三阴性乳腺癌(TNBC)患者更长。全身治疗和全脑放疗(WBRT)延长了所有患者进展为LMD的时间。HR阳性BC患者的激素治疗延迟了BC中枢神经系统转移到LMD的进展。拉帕替尼延迟了HER2阳性BC患者进展为LMD。与HR阳性和HER2阳性的BC-LMD患者相比,TNBC-LMD患者的OS更短。全身治疗、鞘内(IT)治疗和WBRT延长了所有患者的生存期。拉帕替尼和曲妥珠单抗改善了HER2阳性BC-LMD患者的OS。
BC-LMD发病率的上升为临床试验带来了治疗挑战和机遇。迫切需要进行测试拉帕替尼和/或类似酪氨酸激酶抑制剂、IT治疗以及联合治疗的试验。