Abstract P1-17-09: Leptomeningeal disease in ER+HER2- metastatic breast cancer patients: A review of the cases in a single institute over a 14-year period
Authors: Watanabe J , Mitsuya K , Hayashi N , Nakasu Y 
Published: February 2018

Background: Leptomeningeal disease (LMD) is a pattern of central nervous system (CNS) metastasis that occurs in metastatic breast cancer (MBC) patients (pts). Some reports have revealed that it occurs more frequently in pts with estrogen receptor-positive (ER+), HER2-MBC than in pts with other subtypes. However, in such ER+HER2-MBC pts, LMD mainly occurs in the terminal stage of the disease; thus, the details of LMD have not been well described.

Methods: We reviewed the medical records of ER+HER2-MBC pts who were treated from 2002 to present, with the aim of assessing the incidence, background and outcomes of LMD. Statistical analyses were performed using the chi-squared test, Kaplan-Meyer method, log-rank test and a multivariate COX regression analysis.

Results: We identified a total of 369 ER+HER2-MBC pts, and 102 (27.6%) developed CNS metastasis. LMD developed in 32 (8.7%) pts, with the median time to LMD of 778 days (95% confidence interval [CI] 335-1221; range 0-3757 days) from the diagnosis of MBC. In most cases (28, 87.5%), LMD was accompanied by bone metastasis, and 24 pts (75.0%) showed metastasis to the skull. Thirteen pts (40.6%) had accompanying brain metastasis (BM) at the diagnosis of LMD. The majority of the pts had symptoms (25, 78.1%), and their accompanying extra-CNS lesions showed progression (23, 71.9%). Palliative radiotherapy (RT) was introduced in 27 pts (84.4%), with 4 pts (12.5%) receiving whole CNS RT. The intrathecal injection of methotrexate was introduced to one patient. The median overall survival (OS) from the diagnosis of LMD was 104 days (95% CI 38-170); however, when limited to pts without BM (N = 19), the median OS was 146 days (95%CI 79-213). All of the pts died, and the causes of death were as follows: CNS lesion progression, n=10 (31.3%); cachexia, n=9 (28.1%); respiratory failure, n=8 (25.0%); hepatic failure, n=4 (12.5%) and infection, n=1 (3.1%). There was no significant relationship between the time to LMD and OS after the diagnosis of LMD (Spearman's ρ=0.55, not significant). The multivariate analysis did not reveal any specific factors—such as the patient age, the presence of any symptom(s) at the diagnosis of LMD, the distribution of extra-CNS lesion(s) or the control of extra-CNS lesion(s)—that affected OS after the diagnosis of LMD.

As a control, 70 ER+HER2-MBC pts who developed BM without LMD (BM-only group) within the same observation period were analyzed. The median time to BM was 611 days (95%CI 404-818), and it did not differ from that of pts with LMD (LMD-group) to a statistically significant extent (P &gt;0.1). The BM-only group showed superior OS after the diagnosis of their CNS lesions in comparison to LMD-group (median, 295 days and 104 days, respectively, P &lt;0.001). At the diagnosis of the CNS lesion, the LMD-group showed a higher rate of CNS symptoms (P &lt;0.01), a lower rate of liver metastasis (P &lt;0.05), a higher rate of bone metastasis (P &lt;0.05) and a higher rate of skull metastasis (P &lt; 0.01).

Conclusion: Our retrospective analysis at a single institute revealed that the prognosis of LMD in pts with ER+HER2-MBC was still extremely poor. The data suggest that LMD is distinct from BM in terms of its pathology and response to therapy.

Citation Format: Watanabe J, Mitsuya K, Hayashi N, Nakasu Y. Leptomeningeal disease in ER+HER2- metastatic breast cancer patients: A review of the cases in a single institute over a 14-year period [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 P1-17-09.