From the Guidelines
Leptomeningeal disease occurs in approximately 5% of breast cancer patients, with varying rates depending on the breast cancer subtype, and carries a poor prognosis with a median overall survival of approximately 4 weeks, which can be prolonged to a few months with aggressive multimodal treatment. The incidence of leptomeningeal disease is increasing as patients live longer with metastatic disease and as brain imaging techniques improve 1.
Risk Factors and Diagnosis
The condition typically presents late in the disease course, with about 70% of cases occurring after prior metastases to other sites. Risk factors include younger age, higher tumor grade, and prior brain metastases. Diagnosis requires clinical evaluation, cerebrospinal magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis 1.
Treatment Options
Available active treatment options are radiation therapy (RT), intra-CSF therapy, and systemic therapy. The choice of treatment should always involve multidisciplinary discussion. The European Association of Neuro-Oncology (EANO) and ESMO have proposed classifying leptomeningeal disease using two major criteria: presence or not of positive CSF and neuroimaging findings 1.
Recent Guidelines and Recommendations
Recent data suggest that systemic pharmacotherapy, such as the combination of tucatinib, trastuzumab, and capecitabine, or trastuzumab deruxtecan (T-DXd), could have a role in the treatment of patients with leptomeningeal disease, with median overall survival ranging from 11.9 to 13.3 months in some studies 1. The treatment of leptomeningeal disease should be individualized, taking into account the patient's life expectancy, tumor biology, and previous treatments, with a focus on improving quality of life and overall survival.
Key Considerations
The use of intrathecal therapy is controversial and should be considered in cases where tumor cells are present in the CSF, while focal RT and whole-brain RT may be considered for circumscribed or extensive nodular leptomeningeal disease, respectively 1. The prognosis of patients with HER2-positive breast cancer and leptomeningeal disease is poorer than in those with active brain metastases, with estimates of overall survival ranging from 4.4 to 20.0 months 1.
Clinical Implications
In clinical practice, the management of leptomeningeal disease requires a multidisciplinary approach, with consideration of the patient's overall health, tumor characteristics, and previous treatments. The goal of treatment should be to improve quality of life and overall survival, while minimizing toxicity and optimizing symptom management. Further research is needed to improve our understanding of leptomeningeal disease and to develop more effective treatment strategies for this challenging condition 1.
From the Research
Rates of Leptomeningeal Disease in Breast Cancer
- The rate of leptomeningeal disease in breast cancer patients is approximately 5% 2, 3.
- Leptomeningeal carcinomatosis is defined as infiltration of the leptomeninges by metastatic carcinoma, and it remains the most common etiology of leptomeningeal disease in breast cancer patients 2.
- Lobular carcinomas have a higher propensity to metastasize into the meninges compared to ductal carcinoma, especially the triple-negative subtype 2.
Clinical Characteristics and Treatment Outcomes
- The median time from breast cancer diagnosis to development of leptomeningeal disease is around 4.3 years 4 to 16.4 months 5.
- The median overall survival from the diagnosis of leptomeningeal disease to death is approximately 4-5 months 2, 6, 5.
- Treatment outcomes vary by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC 5.
- Patients who received CNS-directed therapy lived longer than those who did not 5.
- Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy 3.
Prognostic Factors
- Performance status at diagnosis, CSF protein level, and triple-negative subtype are associated with poor survival 2.
- Triple negative histology, concomitant brain metastases, and leptomeningeal disease involving both the brain and spinal cord are associated with poor overall survival 6.
- Having TNBC is associated with shorter overall survival from the time of leptomeningeal disease diagnosis to death 5.