BACKGROUNDImprovements in systemic therapies have led to significantly improved survival in patients with breast cancer and have created a challenge with regards to management of brain metastases (BM) and leptomeningeal disease (LMD). LMD is a highly aggressive condition, resulting in rapid neurological decline and a short survival of weeks to months. The purpose of this study is to identify clinical factors that can predict for LMD when a patient is diagnosed with BM, and to assess outcomes with various treatment modalities.METHODSA retrospective analysis was conducted using a clinical database at a single institution and included 178 patients with breast cancer and treated BM between 2007-2020. Demographic, clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cytology or neuroimaging. Chi-square and t-test were used.RESULTSOut of 178 patients with breast cancer and treated BM, 41 (23%) developed LMD. Median age for the study cohort was 51.3 +-13.4 years; those with LMD was 47.9 +-12.3 (p=0.057) years. One of the 178 patients was a male and all 41 with LMD were females. There were 58.5% Caucasian women in the LMD group followed by African-American being 24.4% (p=0.31). Characteristics like number of brain lesions (p=0.57), median size of the largest brain lesion (p=0.70), hemorrhagic/cystic lesions (p=0.68), systemic disease being progressive in 42.6%, stable in 19.3% and 26.1% with no evidence of systemic disease at the time of diagnosis of BM (p=0.34) did not pose a higher risk in developing LMD. For 29% patients the brain lesions were supratentorial, 23.7% were infratentorial and 47.4% patients had both and had a higher risk for LMD (p=0.025). Patients with liver (p=0.45) and bone (p=0.48) lesions did not have higher risk for LMD which was seen in those without lung metastases (p=0.03). In the LMD group, 39% had HR+, 31.7% HER2+, and 41.4% had triple negative breast cancer (TNBC). The higher incidence of HR+ patients could be attributed to the fact that the more aggressive HER2+ and TNBC patients may have not gotten treatment for their BM as they pursued comfort care status. In the LMD group, 13.1% received prior stereotactic radiation, 39.5% whole brain radiation, 10.5% had surgery alone and 36.8% had surgery with pre/post-op radiation. Patients who had any surgery did not have a higher risk for LMD (p=0.26). Surgery did not pose a higher risk for local recurrence, seen in 28% patients (p=0.42) and occurrence of BM at another site, seen in 36.5% patients (p=0.16). CONCLUSIONSAmong breast cancer patients with brain metastases those who develop LMD tend to be younger, with higher risk in Caucasians and African-American women; however, this was not statistically significant. The number, size, hemorrhagic/cystic character of brain lesions did not pose a higher risk whereas occurrence of synchronous lesions in supratentorial and infratentorial locations increased risk of LMD. There was no statistically significant difference in the rates of LMD, local recurrence, CNS recurrence at another site with surgery and/or radiation.

EthnicityBrain metastases (N=178)LMD group (N=41) (p=0.31)
Caucasian 58.4% 58.5% 
Hispanic 12.4% 4.9% 
African-American 19.1% 24.2% 
Others 10.1% 12.2% 
EthnicityBrain metastases (N=178)LMD group (N=41) (p=0.31)
Caucasian 58.4% 58.5% 
Hispanic 12.4% 4.9% 
African-American 19.1% 24.2% 
Others 10.1% 12.2% 

Clinical characteristicsBrain metastasesLMD groupP value
Number of brain lesions (Median interquartile range) 3 (1-8) 2.5 (1-9) P=0.57 
Median size of the largest brain lesion (cm) 2.4 1.4 2.53 1.69 p=0.70 
Hemorrhagic lesions 22 P=0.68 
Cystic lesions 16  
Clinical characteristicsBrain metastasesLMD groupP value
Number of brain lesions (Median interquartile range) 3 (1-8) 2.5 (1-9) P=0.57 
Median size of the largest brain lesion (cm) 2.4 1.4 2.53 1.69 p=0.70 
Hemorrhagic lesions 22 P=0.68 
Cystic lesions 16  

Citation Format: Akshjot Puri, Charisma Mylavarapu, Jiagiong Xu, Tejal A Patel, Bin S Teh, Ivo Tremont-Lukats, Jenny C Chang, Polly Niravath. Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-08.