Leptomeningeal breast cancer metastases: clinical and cytological features on the background of intrathecal methotrexate therapy

Background. Cytological examination of cerebrospinal fluid (CSF) and the dynamics of neurological symptoms are key in the diagnosis and evaluation of treatment effectiveness for leptomeningeal metastases. Quantitative assessment of circulating tumor cells in CSF is not routinely used. This study examined the correlation between the dynamics of tumor cell counts in CSF and the dynamics of neurological symptoms in patients with leptomeningeal metastases from breast cancer during intrathecal methotrexate therapy.

Aim. To identify clinical and cytological features in patients with leptomeningeal metastases from breast cancer during intrathecal methotrexate therapy.

Materials and methods. A retrospective analysis of 30 patients with leptomeningeal metastases from breast cancer who received intrathecal methotrexate in the Department of Neurooncology of the N. N. Blokhin National Medical Research Center of Oncology from 2018 to 2024.

Results. All 30 cases involved women with ductal or lobular breast cancer. The highest proportion of patients with leptomeningeal metastases were found in stage III–C breast cancer (33.3 %). Cytological analysis of cerebrospinal fluid and neurological status assessment were performed before each methotrexate administration. The correlation was monitored throughout the treatment period. A direct statistically significant relationship has been found between the number of tumor cells in cerebrospinal fluid and the severity of neurological disorders: at one month after treatment start r = 0.702; p = 0.000 and at two months r = 0.819; p = 0.000. However, prior to therapy initiation there was no correlation between these parameters (r = 0.056; p = 0.770). Thus, with a low level of tumor cytosis pronounced neurological symptoms could be present (75 cells, symptom score – 6 points), while conversely, with an elevated cytosis level mild neurological manifestations might occur (400 cells, symptom score – 3 points). It was found that only with a decrease in the number of tumor cells in the cerebrospinal fluid by 2 or more times (or by 50 %) does the severity of neurological disorders change. And an increase in the severity of neurological disorders occurs in the case of an increase in the number of cells in the cerebrospinal fluid by 1.2 times (or by 20 %). Moreover, this correlation was maintained throughout the treatment.

Conclusion. Evaluation of the dynamics of tumor cytosis in the cerebrospinal fluid, along with clinical characteristics, can be recommended for use in predicting the response to treatment in patients with leptomeningeal metastases of breast cancer.

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