Improvements in the systemic treatment of patients with metastatic breast cancer (MBC) and the inefficiency of many drugs in crossing the blood brain barrier have led to an increased incidence of symptomatic CNS metastasis. CNS metastases are clinically characterized by two distinct phenotypes, solid CNS metastasis and leptomeningeal metastases (LM). In addition to its poor prognosis, neurological impairment in LM is devastating. No major advances have been made in the treatment and diagnosis of LM, which remains challenging due to low sensitivity of CSF cytology and/or unequivocal MRI findings.
27 pts were diagnosed with breast cancer related LM and treated with IT therapy from 2008 - 2018 (GZA Hospitals Sint-Augustinus, Belgium). Conventional diagnosis was based on positive cytology on CSF and/or the combination of clinical signs and neuro-imaging findings. For a subset of pts (n = 12), circulating tumor cells (CTC) and CSF disseminated tumor cells (DTC) at time of LM diagnosis were enumerated, using the CellSearch platform (Menarini Silicon Biosystems).
The median OS from LM diagnosis was 27 months (4.5-128). Coexisting brain metastases are present in 37% of pts. The biochemical data matched the classic CSF findings of LM including a high protein concentration (75%, 9/12) and a low glucose concentration (42%, 5/12). CSF lactate was elevated (>2.2 mmol/L) in 100% (10/10). In 70% (7/10) CSF lactate was >3.5 mmol/L. Cytologic evaluation of the CSF demonstrated unequivocal malignant cells in 10/12 (83%). DTC enumeration in the CSF of these pts, however, revealed the presence of tumor cells 12/12 (100%). The cell count ranged between 10 - 3523 Epcam+cells/mL CSF.
Symptomatic LM in patients with MBC has a variable prognosis, with some patients experiencing prolonged survival. CSF lactate is a sensitive but aspecific marker of LM. Epcam-based DTC enumeration in the CSF is a robust tool to diagnose LM with apparently a superior sensitivity over conventional cytology. It furthermore has a broad dynamic range rendering it more suitable for treatment effect evaluation. This methodology should be considered in routine workup in MBC patients with suspected LM.
GZA Hospitals Sint Augustinus.
Has not received any funding.
All authors have declared no conflicts of interest.