Abstract P1-17-04: Clinical presentation and outcome of leptomeningeal metastasis in patients with breast cancer in relation to histology and tumor subtypes
Authors: Griguolo G , Pouderoux S , Dieci MV , Jacot W , Bourgier C , Miglietta F , Firmin N , Conte P , Viala M , Guarneri V , Darlix A 
Published: February 2018

Background: Among solid tumors, breast cancer (BC) is one of the most common cause of leptomeningeal metastases. Leptomeningeal disease (LMD) typically carries a devastating prognosis; however, disease presentation and prognostic factors are still uncertain. The aim of this study was to characterize clinical features of LMD in relation to BC histology and subtypes.

Patients and Methods:104 patients (pts) with LMD from BC diagnosed between 2002 and 2017 at two European institutions were included. LMD diagnosis was based on the presence of neoplastic cells on cerebrospinal fluid examination and/or radiological evidence of LMD. Patients' characteristics and their associations with time from LMD to death or last follow up were evaluated by the Kaplan-Meier method, log-rank tests, and Cox proportional hazard models.

Results: Median age at LMD diagnosis was 56 yrs (range 26-75). Tumor histology (n=102) was ductal in 72 pts (70.6%), lobular in 22 (21.6%) and other histology in 8 (7.8%, including mixed ductal and lobular tumors). Tumor phenotype distribution was as follows: hormone receptor (HR)+/HER2- 54.8%, triple-negative (TN) 14.4%, HR+/HER2+ 12.5%, HR-/HER2+ 6.7% and unknown 11.5%. LMD diagnosis was cytologically proven (n=64, 62.7%) and/or radiologically proven (n=88, 85.4%). At time of LMD diagnosis, 63 pts (58.9%) had an ECOG performance status (PS) ≤ 2. 91 pts (87.5%) had extra-CNS disease localizations and 20 (18.7%) had a history of known BC brain metastasis (BM) (predating LMD diagnosis of more than 30 days). In lobular BC, LMD diagnosis was more frequently made in the absence of a known history of BM compared with ductal BC (95.5% vs 73.3%, Fisher test p=0.036). A majority of pts was treated with intrathecal (n=59, 55.1%) or systemic treatment (n=73, 68.2%) after LMD diagnosis, while only a minority underwent radiotherapy (n=28, 26.2%) or surgical derivation procedures (n=14, 13%). Median overall survival (OS) from LMD diagnosis was 3.2 months (95% CI, 1.9-4.4 months). No significant difference was observed across tumor phenotypes, with HER2+ subgroups experiencing better outcomes (median OS: 2.9, 1.6, 6.6 and 12.9 months in HR+HER2-, TN, HR+HER2+ and HR-HER2+ subgroups; p=0.54). In univariate analysis, ECOG PS ≤ 2 at LMD diagnosis, intrathecal treatment and systemic treatment after LDM diagnosis were significantly associated with an improved OS (see table). Multivariate analysis showed that only ECOG PS ≤ 2 and systemic treatment after LMD diagnosis were independent factors associated with OS (see table). Updated results on an extended cohort of about 150 patients total will be presented at the meeting.

  UnivariateMultivariatePrognostic factorsMedian OS in months (95%CI)HR (95%CI)pHR (95%CI)pECOG PS     0-25.9 (2.1-9.7)0.43 (0.27-0.66)0.0010.64 (0.4-1.0)0.06≥31.7 (1.2-2.3)ref ref Intrathecal treatment     Yes5.3 (1.9-8.7)0.65 (0.43-0.98)0.0370.89 (0.57-1.38)0.6No1.9 (0.5-3.3)ref ref Systemic treatment     Yes7.3 (4.7-9.8)0.13 (0.08-0.22)&lt;0.0010.16 (0.09-0.29)&lt;0.001No1.0 (0.6-1.3)ref ref 

Conclusions: LMD carries a dismal prognosis. The results of this series highlight that patient-related features and treatments (in particular the use of systemic treatment) contribute to modulate the prognosis of BC pts with LMD.

Citation Format: Griguolo G, Pouderoux S, Dieci MV, Jacot W, Bourgier C, Miglietta F, Firmin N, Conte P, Viala M, Guarneri V, Darlix A. Clinical presentation and outcome of leptomeningeal metastasis in patients with breast cancer in relation to histology and tumor subtypes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-04.