Abstract P6-13-05: Differences of Clinical Manifestations and Therapeutic Outcomes in Leptomeningeal Metastases (LM) According to Breast Cancer Subtypes
Authors: Lee S , Nam DH , Lee JI , Park W , Choi DH , Huh SJ , Park YH , Ahn JS , Im Y-H. 
Published: April 2011

Abstract
Backgrounds: Breast cancer is the solid tumor most commonly associated with leptomeningeal metastases (LM). Therapeutic modalities include intrathecal and systemic chemotherapy, radiotherapy and other palliative modality including placement of a ventricular reservoir. The aim of this study is to characterize clinical feature and outcomes of LM according to breast cancer subtypes in conjunction with whole CNS metastases.
Methods: A retrospective study was performed on breast cancer patients with LM who received palliative management at Samsung Medical Center between 1994 and 2008. Among 281 metastatic breast cancer patients, 71 breast cancer patients with LM were identified. They were divided into three biological subgroups. The propensity of biological subtypes for LM, clinical manifestation including recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class, and therapeutic outcomes were assessed.
Results: The median age was 48 (range 26-70) years. The rates of the patients with triple negative breast cancer (TNBC), human epidermal growth factor receptors 2 (HER2)-positive and hormone receptor (HR)- positive subtype breast cancer were 26 (44%), 15 (25%) and 18 (31%), respectively. Sixty-four patients (90%) had metastatic disease at sites other than LM. TNBC were more common in RPA RTOG prognostic class III than those in HER2 and HR-positive subtypes (61% vs 39% vs 0%, P&lt;0.0001). CNS including LM was the first site of distant metastasis in 65% of the TNBC patients. Treatment includes intrathecal chemotherapy (IT), whole brain radiotherapy (WBRT), and systemic chemotherapy. The median survival duration from the diagnosis of LM to death (OS-LM) was 4.5 months (range 0.2-26.4 months). Main causes of death were deterioration of neurologic sequelae associated with LM (55%), systemic disease progression (27%), and et cetera (18%). Death rates related with LM at each subtype were 64% for TNBC, 36% for HER2-positive, and 0% for HR-positive patients (p=0.060). In the univariate analysis, RPA RTOG classification (p=0.003), systemic disease control at LM (p=0.041), cytologic negative conversion to IT (p=0.001), systemic chemotherapy after LM diagnosis (p=0.002), and combined modality for LM treatment (p=0.005) were singled out as having prognostic value for OS-LM. Cox-regression multivariate analysis showed that RPA class (HR (Hazard Ratio) 1.8, p=0.022), cytologic negative conversion to IT (HR 0.4, p=0.043), and systemic chemotherapy (HR 0.24, p=0.004) are identified as independent prognostic factors.
Conclusion: TNBC and HER2-positive breast cancer appeared to have special predilection for LM as well as brain parenchymal metastases. High RPA class of TNBC may reflect more aggressive tumor biology in this sanctuary area. OS-LM depended on RPA class, cytologic negative conversion, and the use of systemic chemotherapy. The role of systemic chemotherapy and active local treatment modalities according to subtypes should be defined to improve dismal prognosis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-13-05.